Q2 2020 Agenus Inc Earnings Call

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Good morning, ladies and gentlemen, thank you for standing by and welcome to the agenda second quarter 2020 conference call and webcast. At this time all participants are they listen only mode should you need assistance. Please signal conference specialist.

Operator: Ladies and gentlemen, thank you for standing by, and welcome to the Agenus 2nd Quarter 2020 conference call and webcast. At this time, all participants are in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on your touchtone phone. To withdraw your question, please press star, then two. Please note, this event is being recorded. I would now like to turn the conference over to Dr. Jennifer Buell, President and Chief Operating Officer of Agenus. Dr. Buell, please go ahead.

I've seen the Starkey followed by zero. After today's presentation, there will be an opportunity to ask questions to ask a question. You May Press Star then one on your Touchtone phone withdraw. Your question. Please press Star then too. Please note. This event is being recorded I'd now like to turn the conference over to Dr., Jennifer Bewley, Vice President and Chief.

Keith operating off operate officer of Agenuss Dr. appeal. Please go ahead.

Dr. Jennifer Buell: Thank you very much. Thank you for joining us. Today's call is being webcast and will be available on our website with accompanying slide material for replay. Before we start, we'd like to remind you that this call will include forward-looking statements, including statements regarding our clinical development, regulatory, and commercial plans and timelines, as well as timelines for data release and partnership opportunities. These statements are subject to risks and uncertainties, and we refer you to our SEC filings for more details on these risks. As a reminder, this call is being recorded for audio broadcast.

Thank you very much thanks for joining us todays call is being webcast and will be available on our website with our a company like materials are we play.

Before we start we'd like to remind you that this call will include forward looking statements, including statements regarding our clinical development regulatory and commercial plans and timeline as.

Well its timelines for data release and partnership opportunities.

These statements are subject to risks and uncertainties and we refer you to our FCC filings for more details on these reps.

As a reminder, this call is being recorded for audio broadcast.

I'm, Jennifer if Youre, President and Chief operating officer of agenda, and we are delighted to provide an update today on our business.

Dr. Jennifer Buell: I'm Jennifer Buhl, President and Chief Operating Officer of Agenus, and we are delighted to provide an update today on our business. Joining me are Dr. Garo Armen, Chairman and Chief Executive Officer, Dr. Dan Chan, Head of Drug Discovery, Julie DeSander, Vice President and Head of Business Development, and special guests, Dr. Brie Wilkie, Director of the Sarcoma Translational Research Program at the University of Colorado Cancer Center, and Dr. Chuck Drake, Professor and Co-Director of the Cancer Immunotherapy Programs at New York Presbyterian and Columbia University. Dr. Wilke is one of the foremost experts in sarcoma and the first clinical investigator to dose patients with xelafilamab, our anti-CTLA-4 antibody, in a phase one clinical trial. And she's the senior author on a 2019 publication reporting on the curative benefits of xelafilamab in patients with aggressive angiosarcoma. And Dr. Drake is an internationally renowned expert in immune therapy, immune modulating antibodies, and tumor microenvironment conditioning agents. I'm thrilled to have them with us today. Now, I will turn the call over to Garo to highlight our key achievements in the first half of 2020.

Joining me are Dr., Carl Armen, Chairman and Chief Executive Officer.

Dr., Dan Chen head of drug discovery, Julie to Sander, Vice President and head of business development.

And special guest duct every wilkie director of this I call. My Translational research program at University of Colorado Cancer Center, and Dr., Chuck Drake Professor and co director of the cancer immunotherapy programs in New York Presbyterian in Columbia University.

[laughter] Dr. Wilkie is one of the foremost experts in sarcoma.

First clinical investigator to dose patients with Xcel following up our anti CD only for antibody and a phase one clinical trial and she is the senior author on a 2019 publication to report on the curative benefit as Dallas Allomap in patients with aggressive angiosarcoma.

And Dr. Drake isn't internationally renowned expert in immune therapy immune modulating antibodies and tumor microenvironment conditioning agent I'm thrilled to have them with us today.

No I will turn the call over to go out to highlight our key achievements in the first half 2020.

Garo H. Armen: Thank you, Jen, and thank you all for your interest in Agenus and for joining us this morning. Our special thanks, as Jen mentioned, to our experts, Dr. Drake and Dr. Wilkie, for taking the time from their busy practices to review and interpret the latest data from our trial. Both Bree and Chuck have been extremely helpful with their guidance for rapid clinical development paths for our potentially life-saving medicine. This year... We have advanced our extensive clinical, as well as near-clinical pipeline of agents. We have generated important data updates, some of which we will share with you today. You can also expect additional updates on up to five of our programs. In upcoming presentations at major conferences between now and year-end. Before we go into some of the details,

Thank you again.

Thank you all for your interest in the Genesis and for joining US This morning.

Our special things as Jim mentioned into our exposure stoppage, Craig and I don't know people, taking the time.

Did busy practice to review and interpret the lead to state that from our trials.

Oh, sorry, and shops has been extremely helpful with their guidance for rapid clinical development, so loud potentially lifesaving medicines.

This year.

We have advanced our extensive clinical as well as new clinical pipeline of agents.

We have generated important data update somewhat which you will we will share with you today.

You can also expect additional upstage.

On up to five of our programs.

Upcoming presentations at major conferences between now and you.

Before we going to some of the details.

Garo H. Armen: Please keep in mind that Agenus should be considered fundamentally a technology and biology company. This has allowed us to design our broad portfolio to address one simple thing. How to overcome the challenges posed by cancer, which is constantly trying to evade the bodies in music. This is cancer's big trick, right? This ability of ours is what makes your company special, and our portfolio of innovative products very exciting.

Keep in mind that agenda.

Be considered as fundamentally it technology and biology company.

This has allowed us to design outboard portfolio.

To address one simple thing.

How to overcome the challenges posed by cancer.

Which is constantly trying to evade the body's immune system.

It is cancers big trip by the way.

Disability.

This is what makes your company space.

And our portfolio with innovative products.

Very excited.

[noise] using this intrinsic understanding of the immune system.

Garo H. Armen: Using this intrinsic understanding of the immune system and our portfolio of agents, we expect to transform Agenus into a U.S. commercial biotechnology company, with a recurrent pipeline of innovative immuno-oncology agents. We expect our first two commercial products to be our anti-PD-1, which we call Bali, and our entire CTOA floor, Zali. In addition to investing in innovation.

And our portfolio regions.

We expect to transform agendas into way your west commercial Biotechnology company.

With a week pipeline bald innovate to immuno oncology age.

[noise], we expect our first two commercial products to be our anti PD one.

We called BOLI, and now and I see two away for Sally antibodies.

In addition to investing in innovation.

Garo H. Armen: Early on, we made a strategic decision to develop our own PD-1, Bostolema. We consider PD-1 to be an essential component for use in cocktails with our pipeline of innovative agents. Although there are several commercially available PD-1s and others in development, there are significant advantages to having your own PD-1. The first of these is affordability and flexibility in developing combinations. I want to make a list for you. Our pipeline, our I.O. pipeline, which is synergistic with PD-1, and Derek Statham. [inaudible]

Early on we made a strategic decision to develop our own PD, one well still.

We consider PD, one and B and essential component for use in COPD deals with our pipeline <unk> innovative agents. Although there are several commercially available PD ones and others in development.

There are significant advantages to having your own PD one.

The first so this is affordability and flexibility or developing combinations.

I want to list for you.

Oh pipeline, our I O pipeline, which is synergistic with PD one.

And their extensive they include.

Our other late stage agent exactly the Agenuss first generation suitability for that is.

Garo H. Armen: Our other late-stage agent, Zally, the Agenus first-generation CTLA-4, that is, Agent 1181, our multifunctional CTLA-4, which you'll hear about, with some data later on from CHOP. RFC Enhanced Tygic Monospecific Antibody, Agent 1327, with an IND expected to be filed within the next six months. Also, our FC Enhanced Buy Specific Pidget, anybody?

Age and 11 81, our multifunctional city away for which you'll hear about.

With some data made where I'm from truck.

I would if C and enhanced Tidrick mando specific anybody age and 13 27.

With an eye, India expected to be filed within the next six months.

Also our if see enhanced by specific TIGIT anybody [noise].

Age and one was 777.

Garo H. Armen: HN1777, also an expected IND filing in the next six months. Next, agent 1223, a very exciting bispecific antibody in the clinic, but we have not disclosed the details on its bispecific composition of it just yet, and Agent 2373, our CD137-4-1BB molecule, which is in the clinic. And you'll hear about some data from that molecule in a bit. And lastly, our Allogeneic INKT Cell Therapy for Cancer with an IND, which has been cleared already. So all these compounds that I talked about are absolutely synergistic with our PD-1. Another huge advantage of having PD-1 in-house is to control overpricing for these combinations, which is critical because, based on our meetings with over a dozen payer groups so far, there is an implied price ceiling if several novel I.O.L. combinations are required to treat cancer effectively. And that, by the way, is a foregone conclusion that combinations will be required for effective treatment and control.

Also expect that I'd filing in the next six months.

Next age and 12 23, it very exciting by specific antibody in the clinic, which we have not disclose the details on the bi specific composition of it just yet.

And age and 23 73, our city Wanna duty 74, one we'd be molecule, which is in the clinic and you'll hear about some data from that molecule with a bit.

And lastly, our our June eight I NK cell therapy for cancer within I N D, which is been cleared all right. So all this list so comp stat I talked about.

Which is critical because based on our meetings with over a dozen payer groups so far.

There is an implied price ceiling.

If several novel I O combinations are required to be effectively treating cancer and thats. Five away is have forgone conclusion that combinations will be required for effective treatment and control cancer.

In addition to the advantages offered by having our own PD, one for our own portfolio.

Garo H. Armen: In addition to the advantages offered by having our own PD-1 for our own portfolio, it is also becoming clear that other companies who need a PD-1..., to combine with their own pipeline of agents, or their own commercial products, may prefer to use our PD-1, that is, the Agenus PD-1, versus others, for the same reasons that I have cited which benefit us. Let me now reflect on a couple of other things.

It is also becoming clear that other companies, who need a PD one to combine with their own pipeline wages or their own commercial products may prefer to use our PD. One that is the agenuss PD one.

Versus others for the same reasons that I have cited which benefit us.

Let me now reflect on a couple of other things.

Firstly.

Garo H. Armen: In order to move quickly and effectively in the rapidly moving and highly competitive field of immuno-oncology, we need to have in-house downstream capability. In-house, yes, downstream capability. These capabilities include development and manufacturing. Manufacturing, as many of you know, is becoming a bigger bottleneck for other companies as a result of the demands, particularly lately, imposed on the system due to a substantial number of COVID-19 products and the Government Program. Having our own CMC and manufacturing capabilities allows us to bypass these systemic busts. For example, we have already proactively produced commercial grade Bali and Zali, required for our CMC module expected to be submitted to the FDA in this quarter as part of our expected BLA filing this year. PD-1 antibodies have already generated significant value for several companies, and we believe that There will also be a significant opportunity for us in a market that today exceeds $22 billion in annual revenues with projections that double those numbers in the next five years. That has become exceedingly clear.

In order to move quickly and effectively the rapidly moving and highly competitive field of immuno oncology.

We need to have in house downstream capabilities in house, yes downstream capabilities.

These capabilities include development and manufacturing.

Manufacturing as many of you know is becoming a bigger bottleneck for other companies as a result of the demand, particularly lately imposed on the system due to a substantial number of August 19 products and development program.

James.

Having our own CMC and manufacturing capabilities allows us to bypass the systemic bottlenecks.

For example, we have already pour actively produced commercial grade valliant Sally required for our CMC module expected to be submitted to the FDA in this quarter as part of our expected BLA filing this year.

Second.

PD, one antibodies have already generated significant value for several companies.

We believe there will be also a significant opportunity for us in a market that today exceeds 22 billion in annual revenues when projections, which doubled those numbers in the next five years.

That has become exceedingly clears.

And also very important as I mentioned earlier.

Garo H. Armen: And also, very important, as I mentioned earlier, is that in order to penetrate this large market in a meaningful fashion, with a new PD-1 such as ours, one needs to offer a value proposition with combinations that can provide superior patient benefit. By the way, for those of you who have visual capabilities, we have a series of slides, as you can see on the screen, which are position-appropriate, talk-appropriate, as I go through this.

Is that in order to penetrate this large market in a meaningful fashion.

Within new 81, such as ours, one needs to offer a value proposition with combinations, which can provide superior patient benefit.

By the way for those of you have visual.

Capabilities, we have a series of us.

Slides as you could see on the screen, which are positioned appropriate pocketbook creatives I go through this.

Garo H. Armen: She's gone. In our clinical and neoclinical pipeline, we have several molecules with the potential to offer superior benefit to patients when combined with our PD-1, as I discussed a bit ago. Hence, having our own PD-1 is critically important for our own overall commercial strategy, including, very importantly, the optimization of the revenue potential of our own PD-1 Valley.

His comments.

In our political and near clinical pipeline, we have several molecules with the potential to offer superior benefit to patients when combined with our PD, one as I discussed a bit of critical hence having our own PD one.

Is critically important for our own overcome overall commercial success.

Including the importantly, the optimization of the revenue potential of our own PD One valley.

Today, there's only one commercially available PD one for a city lay for company.

Garo H. Armen: Today, there is only one commercially available PD-1 for SCTLA-4 combination. It is approved in six cancer indications with expected combined revenues of about $13 billion this year, based on data available today.

It is approved than six cancer indications with expected combined revenues of about 13 billion. This year.

Based on data available to date.

Garo H. Armen: The cancer targets for PD-1 and CTLA-4 combinations are in their commercial infant, as emerging data on this slide suggest curative benefit to patients in potentially more than 20 different types of cancer. We're advancing our PD-1 antibody, Bostilumab, as a monotherapy in combination with Zoliferulumab, our anti-CTLA-4 antibody. As you know, our first target is patients with relapsed refractory cervical cancer who have failed first and second line treatment. As you can see on this slide.

Hence the target for building one city away for combinations are in their commercial infancy.

As emerging data.

On this slide.

Suggest curative benefit to patients in potentially more than 20 different types of cancer.

Yeah.

We are advancing our PD, one antibody, but still a map as a monotherapy in combination with lower throw a map our anti city for antibody.

As you know our first target.

His patients with relapsed refractory cervical cancer.

We have failed first and second line treatments.

As you can see on this slide cervical cancer afflicts about 10000 woman in the US every year.

Garo H. Armen: Cervical cancer afflicts about 10,000 women in the U.S. every year. Currently, approved therapies have limited activity with response rates of 10 to 15 percent and limited durability of response, based on the data we have seen so far in cervical cancer. Our anti-PT1 antibody may offer improved clinical benefit compared to other PT1 antibodies. These results are expected to be presented shortly at an upcoming conference this year.

Currently approved therapies have limited activity with response rate of 10% to 15%.

And with limited durability of response.

Based on the data we have seen so far in cervical cancer.

Our anti PD, one antibody may offer improved clinical benefit compared to other PD one antibodies.

These results are expected to be presented shortly at an upcoming conference this year.

When combined with lower Fluor map, we see improved and longer term responses in cervical cancer patients.

Garo H. Armen: When combined with Zoliferolimab, we see improved and longer-term responses in cervical cancer patients. And when we look at clinical data on squamous cell carcinoma of the cervix, which accounts for 70% of total cervical cancer, We see a doubling of these responses with our product, combination. Agenus commercial plans include providing access, This is a very important point, to all patients with cervical cancer, regardless of their health coverage, and affordable. I am confident we can reach this goal while simultaneously creating significant value for your company.

And when we look at clinical data and squamous cell carcinoma August servings patients, which buyout accounts for 70% of total cervical cancers, we see a doubling of these responses with our products combination man.

Agenuss commercial plans include providing access.

The very important point for us.

So all patients with cervical cancer.

Regardless of their health coverage.

Garo H. Armen: The next slide shows the clinical facts of PD-1 beyond cervical cancer. The combination of anti-CTLA-4 and anti-PD-1 has improved response rates, and, very importantly, durability of response, in more than 14 tumor types so far. While our first indication being pursued is cervical cancer, with our combination as well, we are contemplating developing our PD-1 CTLA-4 composition in indications like non-small cell lung cancer, melanoma, renal cell carcinoma, hepatocarcinoma, and a number of others. Today, I will be providing you with an update on our Phase 1-2 trial with Zali and Zalifurlimab. I know I'm switching between Zali and Zalifurlimab. I don't want to confuse you, but Zali is the short name for Zalifurlimab. So, today we will be providing you with an update on our Phase 1-2 trial of Zali as monotherapy and in patients refractory to PD-1. This is an important and growing population of cancer patients. We have enrolled... 39 patients into our phase 2 study of zoliferolimab in patients who have failed anti-PD-1 therapy. In this trial, we have achieved three partial responses in patients with angiosarcoma, squamous carcinoma of the head and neck, and Neuroquink. In addition, however, we have achieved.

And affordability.

I am confident we can reach this goal.

While simultaneously, creating seen significant value for your company.

The next slide.

Shows the clinical samples of PD, one beyond cervical cancer.

The combination of anti Citilane for anti PD, one has improved response rates.

And very importantly, durability of responses in more than 14 tumor types so far.

While our first indication being pursued in cervical cancer with our combination as well we are contemplating to develop our PD one city lay for couples in indications like non small cell lung cancer melanoma renal cell carcinoma.

Hello, carcinoma, and a number of others.

Today, I will be providing you with an update on our phase one two trial with valley Valla further map I know.

Switching between Sally and sell it further map I don't want to confuse you.

How is the saw shortening or zones.

So.

Today, we will be providing you with an update on our phase one two trial of his alley, as a monotherapy and inpatients refractory to PD one.

This is an important and growing.

Dr. Brie Wilkie: Durable Disease Stabilization, and that means beyond six in 13 patients so far. That represents a 40% clinical benefit rate with our first-generation anti-CTLA-4 antibody for patients for whom there's really no treatment at all. These data build on a growing body of evidence that the addition of CTLA-4 alone in PD-1 failures may provide us with a rapid registration opportunity for Zoethrillumab, as well as extrapolate this to our multifunctional next-generation CTLA for everybody, Agent 1181, who have no treatment options today at all. Also importantly, we continue to see complete and partial responses with zoliferulimab in angiosar We have invited Dr. Bree Wilkie, who is an absolutely world-renowned sarcoma expert who has led the clinical trial initiative at Colorado University, to discuss our data. She was the first physician to treat a patient in our Phase I study with zoliferumab and to report on an early observation of the curative potential of zoliferumab, with or without listilumab, in patients with angiosarcom Thank you for being with us today, Brie, and I turn it over to you. Thank you.

Population of cancer patients.

We have enrolled 39 patients into our phase two study of zeller thriller map.

In patients who have failed anti PD one therapy.

In this trial, we have achieved three partial responses in patients with angiosarcoma.

Wamus carcinoma, all the head and neck.

And Neurocrine cancer. In addition, however.

We have achieved durable disease stabilization and that means beyond six months.

In 13 patients so far.

That represents a 40% clinical benefit rate.

With our first generation anti security for input.

Body for patients for whom there's really no treatment at all.

These data build on a growing body of evidence that the addition of Citi away for alone in PD, one failures may provide us with a rapid registration opportunity for those roadmap as well as we can extrapolate this two hour.

Multifunctional next generation city away for any closing agent or have an 81.

In patients.

Who have no treatment options today at all.

Dr. Brie Wilkie: Thank you so much, Garo and Jen, for inviting me to speak today, and it's wonderful to have the opportunity to speak with all of you about the work that has come out of these amazing molecules and our partnership with Agenus. So, my name is Brie Wilkie.

Also importantly.

We continue to see complete and partial responses with over through map in angiosarcoma.

Rare tumors for which there are no approved therapies.

We have invited Dr. Brean Wilkie, who is an absolutely world renowned sarcoma expired.

Dr. Brie Wilkie: I am the Deputy Associate Director for Clinical Research at the University of Colorado and the Director of the Sarcoma Program here. So, for those of you who may not know, sarcomas are a collectively rare group of over 100 different cancers of bone and soft tissues, and what they all have in common is that they're quite devastating in the metastatic setting, and there are essentially no curative therapies.

Okay has led the clinical trial initiative at Colorado University to discuss our data.

Barry was the first physician to treat a patient without phase one study with solar further map and to report and early observations of the curative potential oversold further map with or without postal the map in patients with angioscore.

Coma, Thank you for being with US today, three and excellent novelty. Thank you.

Thank you so much Carolingian provide immediate speak today and it's it's wonderful to have the opportunity to speak with our view about the work that has come out of these amazing molecules in our partnership with agenda.

Dr. Brie Wilkie: They tend to be refractory to treatment, with overall less than 20% of patients surviving more than five years with metastatic disease. And so immunotherapy for sarcomas is really the next frontier. And we've just begun to explore the activity of IO in these sarcomas. And so, during my early years in Miami, I was part of the Xalaphrela MAP Phase 1 trial, and I was able to observe, for the first time, some absolutely unbelievable responses with CTLA-4, as well as PD-1 antibodies in this disease group. And this actually was so influential that it made me completely change my career and focus on how we can use immuno-oncology to create these amazing responses in all patients with sarcomas. And so that led me to the University of Colorado, where now we have both a laboratory completely focused on the sarcoma microenvironment and immuno-oncology.

Okay I am the WD SNC director preclinical research at the University of Colorado, and the director of the sarcoma program here.

So for those of you who may not know star comments are a collectively rare group of over 100 different cancer.

On the top tissues and what they all have in common is that they're quite devastating I'm in the metastatic setting there are essentially no curative therapies and they tend to be refractory to treatment with overall less than 20% of patient providing more than five years with metastatic disease.

And so immunotherapy first our comments is really the next frontier and we've just begun to explore the activity of Io Andy's.

Comments.

And so during my earlier than Miami I'm I was part of these out with Allomap phase one trial and I was able to observe for the first time, some absolutely unbelievable responses on with retailers for as well as PD, one antibodies and study group and it's actually was so influential that it made me completely change my.

Dr. Brie Wilkie: So I just want to tell you a little bit about angiosarcomas, and I think we have some pictures to go along with this. But angiosarcoma is a blood vessel cancer, and the typical story is that these tend to be elderly patients who notice a purplish bruise or lesion on their scalp or their head and neck. And what happens is they see their dermatologist, it gets biopsied, and comes back as this disease. And like most scalp lesions or skin lesions, the first instinct is to perform surgery to remove it.

Career and focus on how we can use immuno oncology to create these amazing responses to all patients with our comments.

So that let me tell the University of Colorado, where now we have on both a laboratory completely focused on sarcoma microenvironment and immuno oncology.

Dr. Brie Wilkie: So the problem with angiomas is that these tumors are often extremely infiltrative, meaning there are disease deposits well away from the primary lesion. And so these patients undergo these huge, highly morbid, and disfiguring surgeries in an attempt to remove the disease. Unfortunately, the relapse rate is extremely high, probably 70 to 80 percent for larger tumors, and chemotherapies temporarily can provide some benefit, but they are definitely not curative, and patients wind up ultimately succumbing to this disease fairly regularly. And so my 62-year-old patient with angiosarcoma that was treated with valifrelimab in 2015 was one of these patients. So she had an angiosarcoma on her nose, and she went through surgeries, radiation, and about a dozen different types of chemotherapies, targeted therapies, and was really completely out of options with a very disfiguring and aggressive disease. So we enrolled her in the very first dose level of valifrelimab at 0.1 mg per kg, and what we saw is that within 10 to 12 days, her tumor really exploded. It was absolutely unbelievable to see the obvious immune infiltration.

So I just want to tell you a little bit about angiosarcoma and I think we have some pictures tactical along with that.

The angiosarcoma is a blood vessel cancer and the typical story is that these tend to be elderly patients who noted a publish Bruce core lesion often on their scalp or their head and neck and what happens is they see their dermatologists ticket Biopsied and comes back as this disease and.

Like most scalp leasing their skin lesions that first instinct is to perform surgery to remove it.

So the problem with angio is that these tumors are often extremely infiltrate as there are disease deposits well away from the primary lesion and so these patients undergo the huge I'm highly morbid and disfiguring surgeries in an attempt to remove the disease.

Unfortunately, the relapse rate is extremely high probably 70% to 80% for larger tumors and chemotherapies are temporarily can provide benefit but they are definitely not curative.

And patient wind up ultimately succumbing to this disease fairly regularly.

And so my 62 year old patient with angiosarcoma that with treated on Dallas from them out in 2015 with one of these patients.

Dr. Brie Wilkie: And she went on to have improvement in her disease and ultimately achieved a complete response, not just radiographically, but pathologically, by biopsy. And I'm thrilled to say that now, four years later, this woman is essentially cured of her angiosarcoma because of xalophrelomab. And so this was one of the moments where I knew we were on to something big, and I wound up continuing to treat angiosarcomas with either ongoing immuno-oncology studies or potentially off-label for patients with no other options. And so what we wound up doing was publishing a case series of about seven patients at the University of Miami that were treated with either CTLA-4, CD1, or the combination. And so in this paper, we actually showed that at 12 weeks, five of those seven patients had either clinical or radiographic partial responses of their tumors with IO.

She had a angiosarcoma on her knows and she went through surgeries radiation and about a dozen different type of chemotherapy targeted therapies and was really completely out of options with a very disfiguring and aggressive disease.

So we enrolled her on the very first dose level of valley Fella Mab at 0.1 make per head.

And what we size that within 10 to 12 days her tumor really exploded it was absolutely unbelievable to see the obvious immune infiltration.

And she went on to have improvement in her disease and ultimately achieve a complete response, not just radio graphically, but pathologically by biopsy.

And I'm thrilled to say that now today four years later this woman is essentially curative per angiosarcoma because of the valid for Allomap.

And so this was one of the moments where I knew we were onto something big and I wound up continuing to treat angiosarcoma is with either on ongoing immuno oncology studies or potentially off label for patients with no other options.

Dr. Brie Wilkie: We also, in partnership with Agenus, were able to delve into some of the biological mechanisms of our super-responder, and we're happy to make those data available to you. And so because of this amazing response, this has changed my clinical practice, where I've gone on to encourage, as opposed to upfront aggressive surgeries and radiation for angiosarcoma patients, that we actually get these patients on early immunotherapy trials because of this amazing ability to downstage the tumors and potentially give these folks a better outcome. So the common question is, OK, well, this is great, but angiosarcoma is really rare. There are probably only about 200 to 300 cases per year in the United States. But what's important to know is that in other countries, this incidence can be very different, particularly in Asia.

And so what we wound up doing is publishing a case series of about seven patients at the University of Miami and there were treated with either detailee for PD, one or the combination.

And so in this paper, we actually show that at 12 week five of those seven patients had either clinical or radiographic partial responses of their tumors with Io.

We also in partnership with Agenuss, we're able to delve into some of the biologic mechanisms of our Super Responder and we're happy to make those data available to you.

And so because of this amazing response. This has changed my clinical practice, where I've got off to encourage time as opposed to upfront aggressive surgeries and radiation.

For angiosarcoma patients that we actually get these patients on early immunotherapy trials.

Because of this amazing ability to downstage, the tumors and potentially give these folks a better outcome.

Dr. Brie Wilkie: And remember, there are no available treatment options for these patients. And so we're super excited, in partnership with Agenus, that we will be launching a clinical trial, a phase two clinical trial of xalifrelimab with or without valstilumab for patients with angiosarcoma. And this will be in partnership with my colleague, John Trent, at the University of Miami, as well as here at the University of Colorado and across the world. And so this is really the first angiosarcoma-specific clinical trial that will be done with immunotherapy. And I'm incredibly excited about the potential for this. This could potentially lead to an opportunity for an accelerated approval and really change clinical practice and the available treatment options for these desperate patients. So where are we heading in the future?

So the common question is okay. Well this is great, but angiosarcoma is really rare theres, probably only about two to 300 cases per year in the United States, but what's important to know is that in other countries. This incidents can be very different particularly in Asia.

And remember there were no available treatment options for these patients and so we're super excited in partnership with agenda that we will be launching a clinical trial a phase two clinical trial, UBS, LFL AMAP with or without L. still amount.

For patients with Angiosarcoma and this will be in partnership with my colleague John trend at the University of Miami at Wells here at the University of Colorado and across the World and so this is really the first angiosarcoma specific clinical trial that will be done for immunotherapy and I'm incredibly excited about.

So for this.

It could potentially lead towards an opportunity for an accelerated approval and really change clinical practice and the available treatment options for these desperate patients.

Dr. Brie Wilkie: So I told you that angiosarcoma appears to be incredibly sensitive, but what about the rest of these sarcomas out there? We've learned that, like many other cancers, it's really only a fraction of these diseases and a fraction of patients that benefit from PD-1 or CTLA-4 monotherapy. Why is this?

So where are we heading in the future. So I told you that angiosarcoma appears to be incredibly sensitive, but what about the rest of the sarcomas out there we've learned that like many other cancers, it's really only a fraction of these diseases in a fraction of patients that benefit from PD, one or citilane for monotherapy.

Dr. Brie Wilkie: What are the resistance mechanisms that we're encountering? The work that I'm doing in the laboratory suggests that one of the critical components for sarcomas to respond to immuno-oncology agents is that you have to have a robust initial immune response to generate tumor-specific T cells that can then be perpetuated and activated with checkpoint inhibitors. And so, as many of you know, one of the best ways to stimulate that initial tumor immunogenicity is with chemotherapy. And in the sarcoma world, doxorubicin, which has been the standard of care for 40 years but is still only palliative in nature, has been well described in the literature to have potent effects on those early immune responses by inducing type one interferon responses and helping to release danger factors to stimulate that initial antigen recognition.

So why is this what are the resistance mechanisms that were encountering.

The work that I'm doing the laboratory suggests that one of the critical components first our comments to respond to immuno oncology agents is that you have to have a robust initial immune response to generate tumor specific T cells that can then be perpetuated and activated with it with a checkpoint inhibitors.

And so in many of you know one of the best ways to stimulate that initial tumor immunogenicity as with chemotherapy.

And in the sarcoma World Docs are Rubican, which is been a standard of care for 40 years, but still is only pay live in nature has been well described in the literature to have potent effects on those early immune responses by inducing type one interferon responses and helping to release danger factors.

Stimulate that initial antigen recognition.

And so I'm really excited to combine chemotherapy.

Dr. Brie Wilkie: And so I'm really excited to combine chemotherapy along with checkpoint inhibitors, and I think that in sarcoma, this will expand our response rates and potentially durability of the response. And so we have also, with Agenus, launched an investigator-initiated clinical trial that is ongoing now, that's combining doxorubicin plus vali and vali for metastatic soft tissue sarcomas in the first or second line of therapy. And so, as I think you can see on the diagram, we basically prime the sarcoma first with combination PD-1 and CTLA-4 inhibition, and And so I've seen results from the first five valuable patients in this study, and while today I cannot report any official data, I'll simply leave it to say that I'm extremely optimistic about the potential of this study.

Along with checkpoint inhibitors, and I think that in sarcoma. This expand our response rates and potentially durability of the response.

And so I, we have also with Agenuss launched an investigator initiated clinical trial that is ongoing now that combining docs are robison.

Plus Sally and valley for metastatic soft tissue sarcoma is in the first or second line therapy.

And so as the I think you can see on the Sema, we basically prime the sarcoma first with combination PD, one and detailed for inhibition and then we began docs Aruba fan to take full advantage of that initial boost the danger factors and then patients can continue on maintenance therapy.

And so I've seen results from the first five evaluable patients on the study and while today I cannot report any official data all simply leave it to say that I'm extremely optimistic about the potential of this study.

Dr. Brie Wilkie: Since Doxo is really the standard of care, this initial investigation could have the potential to completely change how we treat many types of soft tissue sarcomas. And so, while it's a big dream, I will say that Agenus has never been afraid to think bigger and aim higher with me. And so I'm incredibly excited about the future moving forward. So thank you all for your passion for these rare cancers, for our work, and for helping all patients with cancer. Thank you. Thank you very much.

Since docs. So it's really the standard of care. This initial investigation could have the potential to completely change how we treat many types of soft tissue sarcoma and.

And so while at the Big Dream I will say that Agenuss has never been afraid to think bigger and aim higher with me.

Its I'm incredibly excited about the future moving forward.

Thank you all for your passion for these rare cancers for our work and for helping all patients with cancer. Thank you.

Thank you very much free we congratulate you on your work for your patience, which is quite remarkable.

Julie DeSander: Thank you very much, Brie. We congratulate you on your work for your patients, which is quite remarkable. Now, building value for our lead molecules, we will expand the benefit of CTLA-4 and PD-1 combinations across different tumors, but also, very importantly, across different geographies as well. And while we do not have today the capacity to be all over the world from a commercial perspective, It is critical for us to make sure that we have the right partners to be able to expand globally. A few weeks ago... We now announce our partnership with Beta Pharmaceuticals, a national-level high-tech pharmaceutical company based in China. Beta has a strong track record of advancing innovative products in China and a growing portfolio of complementary oncology therapies. They are an ideal partner to enable us to address significant patient needs in China, which, by the way, is a rapidly growing market, while also advancing the global development of Balsillimab and Zoliferolimab. I will turn the call over to Julie DeSanders, the head of all of our business development efforts, to highlight the strategic value of this partnership.

Now building value for our lead molecules, we will expand to benefit obviously until a four and PD, one combination say across different tumors.

We're also very importantly across different geographies as well.

And while we do not have today to capacity to be all over the world from a commercial perspectives.

It is critical for us to make sure that we have the right partners to be able to expand globally.

A few weeks ago.

We now in Austin partnership with bed Hot Pharmaceuticals, and national level High intent pharmaceutical company based in China.

Ben has a strong track record of advancing innovative products in China.

And a growing portfolio complementary oncology therapies.

There are an ideal partners will enable us to address significant patient needs in China.

Which by the way is a rapidly growing mark.

While also advancing global development on both filler map as all the for Matt.

I will turn call over to Julie the center.

The head all of our business development expertise to highlight the strategic value is partners Julie.

Thank you narrow as Carol mentioned, a few weeks ago, we announced a new partnership with better pharmaceuticals.

Julie DeSander: Thank you, Garo. As Garo mentioned a few weeks ago, we announced a new partnership with Feta Pharmaceuticals, granting rights to Valfilamab and Xalafilamab in Greater China in exchange for $35 million up front in cash and equity. A hundred million in milestones and tiered royalties up to the low 20s. We're thrilled to expand the benefit of balacelamab and salicelamab to patients in this region. China represents an important geography for Agenus. The PD-1 market in China alone is projected to grow to over $14 billion over the next 10 years, and the addition of CTLA-4 meaningfully improves the efficacy of PD-1 therapy. We expect balcellumab and balacellumab to be the first approved PD-1-CPLA-4 combination in cervical cancer. It was important for us to enter China with a strong local partner who has deep knowledge of the market, regulatory processes, and clinical footprint in the region.

Anything right about telematics developed allomap in greater China in exchange for 35 million upfront in cash and equity.

100 million, a milestone and tiered royalties up to the low twentys ourselves to expand the benefit about filling up and balance allomap patients in this region.

China represents an important geography for agenda.

The PD one market in China alone is projected to grow to over $14 billion over 10 years.

And the addition of CP like more meaningfully improve the efficacy of PD one therapy.

We expect about filling up and Dallas will amount to be the first approved PD, one PD lipar combination in cervical cancer.

It was important right the into China with a strong local partner, who have deep knowledge of the market regulatory processes and clinical footprint in the region.

We feel like Embeda as our ideal partner based on their success in launching the first innovative oncology product in China in lung cancer.

Julie DeSander: We selected BETA as our ideal partner based on their success in launching the first innovative oncology product in China for lung cancer, their commercial footprints, and their broad clinical portfolio that may benefit from combinations with PD-1 or CCLA-4. Together, we look forward to bringing the benefits of balfilamab and xalafilamab to cervical cancer patients in China, which has 10 times the incidence compared to the U.S.

The commercial commercial footprint and their broad clinical portfolio that may benefit from combinations with PD. One once you feel like for <unk>.

Together, we look forward to bringing the benefit about selamat valid one of them out to cervical cancer patients in China, which has 10 times the incidence compared to the U.S.

He will also be exploring label expansion opportunities with better in areas of high unmet need which could include indications such as long gastric or liver cancer.

Dr. Jennifer Buell: We will also be exploring label expansion opportunities with BETA in areas of high unmet need, which could include indications such as lung, gastric, or liver cancer. These indications account for nearly half of all cancer-related deaths in China and are indications where the addition of CPLA-4 significantly improves the efficacy of PD-1 therapy. Finally, we look forward to pursuing new synergistic combinations of these agents with both Agenus and Betis' other pipeline programs. I will now turn the call over to Jennifer to provide an update on the progress of our novel program and upcoming catalyst.

These indications account for nearly half of all came for really the death in China, and our indications where the addition of people really for significantly improved the efficacy of PD one therapy.

Finally, we look forward to pursuing new synergistic combinations of these agents with both agenda and but other pipeline programs.

Well now turn the call over to Jennifer to provide an update on progress of our novel programs and upcoming catalysts.

Thank you very much Julie.

Dr. Jennifer Buell: Thank you very much, Julie. And thank you again, Dr. Wilke. That was an outstanding presentation. We're thrilled to be in a partnership with you. And very exciting to see the maturity of the data from our current trial, our phase two trial of xalophthalimab in refractory patients, patients refractory to PD-1. That trial's in its very early days, but we already have three responses.

[noise]. Thank you again, Dr will keep that was an outstanding presentation, we're thrilled to be in a partnership with you and very exciting to see the maturity of the data from our current trial a phase two trial zealous telematics and refractory patients patients refractory to PD, one that child and it's it's very.

Early days, so we already have three responses, we have clinical benefit rate.

Dr. Jennifer Buell: We have a clinical benefit rate of over 40% with 13 patients with durable disease stabilization, and we're looking forward to the continued maturity of that data, and we're thrilled to be launching a trial specifically in angiosarcoma. Those are really great results, and we're excited about what the future can look like for these patients with such a rare tumor. And I also want to highlight that angiosarcoma is a relatively rare tumor, but it's more prevalent in Asians living in the U.S., of course, but also in China. We see a much higher prevalence of angiosarcoma, so we're looking forward to seeing what we can do for patients globally within our own hands and through our partnership. Now, when you focus on value creation, value is created. And in 2015, we set out on a plan to become a commercial company set up for success. Today, we outline our path to becoming a commercial company. Garo touched on our clinically validated assets, and you've heard some of the data.

Over 40%.

With 13 patients with terrible disease stabilization and were looking forward to the continued maturity of that data and we're thrilled to be launching a child specifically in angiosarcoma. Those are really great results and where were excited about what the future can can apply for these patients with such a rare tumor and I also want to highlight that.

Angiosarcoma Insys is relatively rare tumor, but it's it's more prevalent and Asian living in the U.S. of course, but also in China, we see much higher prevalence of angiosarcoma. So we're looking forward to seeing what we can do for patients globally I'm within our own hands and through our partnership.

[noise] now when you focus on value creation value is created and in 2015, we set out on a plan to become a commercial company set up for success.

Today, we outlined our path to becoming a commercial company.

Got you touched on a clinically validated assets you've heard some of the data you've seen data on these programs earlier this year and you will see more data and upcoming medical conferences later this year.

Dr. Jennifer Buell: You've seen data on these programs earlier this year, and you will see more data at upcoming medical conferences later this year. We also presented the opportunity that Agenus has to drive differentiated value through combinations. At our core, we are technologists and biologists.

We also presented the opportunity that agenuss has to drive differentiated value through combinations.

At our core we are technologists and biologists we've designed the most innovative and productive research engine in our industry with more than 21 assets advancing in preclinical and clinical development 13 are already in the clinic being pursued by Agenuss in some of which are with our collaborators as Julie mentioned, we have than most.

Dr. Jennifer Buell: We've designed the most innovative and productive research engine in our industry with more than 21 assets in preclinical and clinical development. Thirteen are already in clinical development being pursued by Agenus, and some of which are with our collaborators. As Julie mentioned, we have a recent collaboration with BETA, but on slide 13, you'll see that we also have very productive collaborations with Gilead, Urigen, Insight, Merck, and, of course, GSK. Eight molecules are in preclinical development. Some of those you will be seeing moving into the clinic this year.

We think collaboration with that but on slide 13, what you'll see it that we also have very productive collaboration with Gilliat Your engine insight Mark and of course GSK.

[noise] eight molecules are in preclinical development some of those she will be seeing moving into the clinic. This year as Carol mentioned, our allogeneic I N K T cell therapy had been cleared to enter the clinic to treat patients with Kobin 19, as well as patients with cancer and I'll go over our plan.

Dr. Jennifer Buell: As Garo mentioned, our allogeneic INKT cell therapy has been cleared to enter the clinic to treat patients with COVID-19 as well as patients with cancer. And I'll go over our plans for those cells soon. Additionally, Dr. Dan Chan will talk with you about our Tidgit, our family of Tidgit molecules, our FC-enhanced Tidgit monospecific, as well as our FC-engineered Tidgit bispecific program. I want to take a minute to talk a little bit about GSK before I go into our innovative pipeline. GSK has been our longest strategic partner.

For those cells I assume.

Additionally, Dr. Dan channel to talk with you about our ticket our family of TIGIT molecules are FC enhance ticket minus specific as well as our assay engineering TIGIT by specific program.

[noise] [noise] [noise] [noise] [noise] I want to take a minute to talk a little bit about G.S.K. before I go into our innovative pipeline.

[noise] GSK has been our longest strategic partner they launched one of the most successful vaccines in recent times. This is the Qs 21 support and containing Shingrix vaccine.

Dr. Jennifer Buell: They launched one of the most successful vaccines in recent times. This is the QS21 Saponin-containing Shingrix vaccine, which registered revenues of over $2 billion last year. This vaccine, clinically, has demonstrated to be the most effective vaccine with over 90% efficacy, which is enhanced as individuals age, which is not the case with Zostavax, the competing vaccine, which is only 50% efficacious, and the benefit wanes over age. So, as individuals get older, the vaccine is less effective. And this is a really important component.

Which registered revenues of over $2 billion last year.

This vaccine clinically has demonstrated to be the most effective vaccine with over 90% efficacy, which is a enhance and as individuals age which is not the case with zostavax, the competing vaccine, which is only 50% efficacious and if any.

Benefit liens over age so as individual get older. The vaccine is less efficacious and this is a really important component. We think a lot about Qs 21, when we look at the requirements for addressing a pandemic and when we hear that some of our regulators maybe looking at efficacy.

Dr. Jennifer Buell: We think a lot about QS21 when we look at the requirements for addressing a pandemic. And when we hear that some of our regulators may be looking at efficacy of about 50%, we know that vaccines can be more efficacious. We believe that QS21 could be a critical part of that.

We have about 50%, we know that vaccines can be more efficacious.

We believe that Qs 21 could be a critical part of that.

Now overall through our our financial transactions with our partners, we've generated more than $575 million and cash since 2015, and our efforts to finance your company with an eye to minimize dilution well, we support the accelerated deliver delivery of multiple discoveries into.

Dr. Jennifer Buell: Now, overall, through our financial transactions with our partners, we've generated more than $575 million in cash since 2015 in our efforts to finance your company with an eye to minimize dilution while we support the accelerated delivery of multiple discoveries into and through the clinic. Now, tumors have a sophisticated escape pathway, as you've seen some of the illustrations from Dr. Wilkie's presentation, and the gravity that these tumors have when they effectively co-opt systems. These escape pathways are designed to avoid immune detection and thrive.

And through the clinic.

Now tumors have a sophisticated escape pathways you've seen some of the illustrations from Dr. work his presentation and the gravity that these tumors have one effectively collapse system.

These escape pathways are designed to avoid immune detection and thrive.

Our discovery engines designed to keep ahead of cancers pace and deliver high impact therapies for patients with cancer.

Dr. Jennifer Buell: Our discovery engine is designed to keep ahead of cancer's pace and deliver high-impact therapies for patients with cancer. We're focusing on delivering antibodies, cell therapies, and vaccine combinations designed to elicit immune recognition of tumors, so that the immune system can see the tumor, and detect the tumor. Then we enable tumor destruction by immune cells, and we block tumor escape pathways.

We're focusing on delivering antibody cell therapies and vaccine combinations design to a lift that I mean recognition of tumors.

So that the immune system can see the team right detect the tumor then we enable tumor destruction by immune cells and we block tumor escape pathways.

Dr. Jennifer Buell: These include assets that are designed to target myeloid cells, T and NK cells, and a pipeline of molecules that I'm going to go into in just a moment. Our strategy to eradicate cancer is fourfold. We would advance foundational molecules like CTLA-4 and PD-1 designed for optimal combination approaches, and develop molecules to improve upon validated targets like our FC-engineered next-generation CTLA-4 molecule, which is a significant enhancement over currently available anti-CTLA-4 molecules. We seek to block escape mechanisms through innovative molecules and combination approaches, and modulate or condition the tumor microenvironment to eliminate tumor growth.

These include assets that are designed to target myeloid cells T and NK cells, and a pipeline of molecules and I'm going to go into in just a moment our strategy to eradicate cancer is fourfold.

We would advance foundational molecules like see tally for NPD, one designed for optimal combination approaches.

Develop molecules to approve upon validated targets like our FC engineered next generation CTL, they form molecule, which is a significant enhancement over currently available anti sealy for molecules.

We seek to block escape mechanisms through innovative molecule in combination approaches and modulator or condition, the tumor micro environment to eliminate tumor growth.

[noise] Agenuss has all of these components in our pipeline checkpoint antibodies bind specifics allogeneic cell therapy, Qs 21 outage events.

Dr. Jennifer Buell: Agenus has all of these components in our pipeline: checkpoint antibodies, bispecifics, allogeneic cell therapy, and QS21 adjuvant. This gives your company a significant advantage for independence in clinical development as well as in the commercial marketplace, where we will not be vulnerable or limited by established pricing for combinations. We plan to develop, register, and launch our lead programs in the U.S. and seek out-of-U.S. partners in the near term to fully appreciate the value of our late-stage pipeline while we continue to innovate. Our first generation CTLA-4 and PD-1 are poised to be first to market in refractory cervical cancer and potential second to market in larger market opportunities and validated indications such as non-small cell lung cancer, melanoma, RCC, hepatocellular carcinoma, and others such as sarcoma. Our Next Generation Pipeline showcases the features of our technology and innovation. And this is where I believe the genius of Agenus really shines through.

This kisha company, a significant advantage for independence and clinical development as well as in the commercial marketplace.

Where we will not be vulnerable or limited by established pricing for combination.

We plan to develop register and launch our lead programs in the U.S. and she actually less partners in the near term to fully appreciate the value our late stage pipeline, while we continue to innovate.

Our first generation see Chile for him PD, one or pod are poised to be first to market in refractory cervical cancer and potential second to market and larger market opportunities and validated indications such as non small cell lung cancer melanoma, RCC, hepatocellular carcinoma, and others such as sarcoma.

Our next generation pipeline showcases the features of our technology and innovation and this is where I believe the genius of Agenuss really shines through.

Dr. Jennifer Buell: This year, we presented data on Agen 1181. We also presented data on Valstilumab and Xalophrelumab. Today, I'm going to provide you an update on clinical data from our Agen 1181 trial, as well as early phase data from Agen 2373, our differentiated anti-CD137 antibody, and Agen 1223, our intratumoral Treg depleting agent. In addition, I'll discuss our plans to expeditiously launch combinations with these novel agents in the clinic. I will conclude with a summary of data to be presented at upcoming conferences this year.

This year, we presented data on H. and 11 81.

We also presented data on valves telematics and dollar felling.

Today I'm going to provide you an update on clinical data from our Asia 11, 81 trial as well as our early phase data from agent 23, 73, our differentiated anti CD 137 antibody and 810 12, 23 hour Intratumoral T Reg depleting agent.

In addition, I'll discuss our plans to expeditiously lunch combinations with these novel agents in the clinic.

I will conclude with a summary of data to be presented at upcoming conferences. This year.

So first agent 11, 81. This is a multi T cell engaging antibody, which also binds anti CTL. They for its an FC engineered antibody. It's rationally designed to overcome the shortcomings of business Yervoy and other in class anti CTP four antibodies through FC engineering.

Dr. Jennifer Buell: So first, HN1181, this is a multi T cell engaging antibody that also binds anti-CTLA-4. It's an FC-engineered antibody. It's rationally designed to overcome the shortcomings of Bristol-Gervois and other in-class anti-CTLA-4 antibodies through FC engineering and enhanced binding to FC-gamma receptor 3A variants, enabling anti-tumor activity in a larger proportion of patients. We expect to expand benefit to nearly three times the proportion of patients responding to first-generation CTLA-4. This is through enhanced immunogenicity as well as Treg depletion.

And enhance binding to FC gamma receptor three a variance, enabling anti tumor activity and a larger proportion of patients.

We expect to expand benefit to nearly three times the proportion of patients responding the first generation CTL before [noise].

This is through enhanced immunogenicity as well as to rank depletion.

We previously reported on a complete responder at one make part cake monotherapy age and 11 81.

Dr. Jennifer Buell: We've previously reported on a complete responder at one mig per keg monotherapy with Agen 1181. We also reported to you a patient with microsatellite-stable endometrial cancer, PD-L1-negative, who demonstrated an 80% reduction in their target lesions and a complete response in their non-target lesions. These data were presented by Dr. Steven ODay at ASCO.

We also reported to you a patients with microsatellite stable endometrial cancer PDL, one negative who demonstrated an 80% reduction and their target lesions and a complete response and their non target lesion. These data were presented by Dr., Stephen or Dan ASCO.

Dr. Jennifer Buell: Today, I'm thrilled to report that this patient, this previously partial responder, has now been determined to be a complete responder by PET scan technology. These responders, both of these complete responders, have microsatellite-stable endometrial cancer, their tumors are PD-L1 negative, and they both have genetic polymorphisms in their CD16 allele, which renders them unlikely to respond to first-generation CT These data are highlighted on slide 16, and over 60% of patients in this early phase one study. We currently have nine patients who are pending scans out of a total of 36 patients treated to date. Of course, accrual continues, and the trial is now being expanded to target indications. We're really excited about the activity of our first generation CTLA-4 as well as HN1181, our next generation CTLA-4.

Today I'm thrilled to report that this patient. This previously a partial responder has now been determined to be a complete responder by a pet scan technology.

These responders both of these complete responders have microsatellite stable endometrial cancer, there tumors are PDL, one negative and they both have genetic polymorphism in their CD, sixteena leal, which renders them unlikely to respond to first generation CTL LIFO.

Of course.

These data are highlighted on slide 16.

Stabilization and over 60% of patient and its early phase one study.

We currently have nine patients who are pending scan out of a total of 36 patients treated to date of course accrual continues and the trial is now being expanded to target indications. We're really excited about the activity of our first generation Z, Chile for as well as age and eliminating one our next generation would be dealing for.

Okay.

Dr. Jennifer Buell: As Brie mentioned, we've already reported on two responders and patients with angiosarcoma, and Garo shared the Phase II data of zelophthalimab in patients who failed PD-1, with four responders, 13 patients with durable disease stabilization, and the trial is quite early in its development. We see opportunities for strategic development of these agents through selective enrichment of our patients, and that may potentially be, by CD16, allele We have invited Dr. Chuck Drake to share his thoughts on CTLA-4 in general and specifically the differentiation of HN-1181 and the possibilities for this molecule in the landscape of I.O. as well as his interpretation of single agent activity of HN-1181 in advanced refractory cancers. Dr. Drake

As free mentioned, we've already reported on T. responders in patients with Angiosarcoma and got a shared the phase two data is LFL them out in patients who failed PD one with with floor response responders 13 patients with a terrible disease stabilization and other trial is quite early in its development, we see opportunities for strategic.

Element of these agents through selective enrichment ever patients and that may potentially be vice city 16 Electronification.

We have invited Dr., Chuck Drake to share his thoughts on seen ceiling for in general and specifically the differentiation of age and 11 anyone in the possibilities for this molecule and the landscape Io as well as his interpretation of single agent activity, HM 11, 81, and it would be.

Yes refractory cancers.

Dr Drake.

Dr. Chuck Drake: Hey Jen, thank you. I'm very happy to be here. I've been working on immunotherapy since around 2000, really kind of with not much success until about 2007, when I was fortunate to treat the first kidney cancer patient in the world ever with anti-PD-1. That was on a phase one trial, and that patient had a complete response and remains in complete response to this day. But what I can tell you is that seeing complete responses in phase one trials is incredibly rare. And so seeing a pet CR in this setting is really quite interesting and quite unusual, actually.

Hi, Joe Thank you I'm very happy to be or.

I've been working on immunotherapy since around 2000 really kind of what's not much success until about 2007, what I was fortunate to treat the first kidney cancer patient in the world ever with PD. One that was on a phase one trial that patient had a complete response and remains and complete response the stakes, but what I can tell you have seen complete responses.

In phase one trials is incredibly rare and so seeing a pay a pet CR in the shutting is really quite interesting and quite unusual actually as you know phase. One trials are not designed to test activity frankly, they're designed to test safety and so far the data for 11 81.2, very reasonable safety profile, what's really don't have tougher citis.

Dr. Chuck Drake: As you know, phase one trials are not designed to test activity, frankly. They're designed to test safety, and so far, the data for 1181 points to a very reasonable safety profile with really no hypophysitis or severe unexpected immune-related adverse events reported. The other thing that I think wasn't quite highlighted from this trial is that sometimes the immune system doesn't quite eliminate the tumor but enters into long-term disease stabilization. And Garo mentioned that in this trial, there were a large number of patients with stable disease. And when people say stable disease, they usually just say it specifically. But if you remember, Garo said it perfectly.

[noise] severe unexpectedness immune related adverse events reported on the other thing that I think I wasn't quite yet how highly to from this trial is.

Sometimes the immune system doesn't quite eliminate the tumor but enters into a long term disease stabilization and Karl mentioned that on this trial. There were a large number of patients with a stable disease and wouldn't where people say stable disease. They usually just say what specifically, but if you remember Gallagher said it perfectly these patients had stable disease for.

Dr. Chuck Drake: These patients had stable disease for greater than six months. So six months is not usually seen in phase one trials, and that really does reflect early evidence of clinical activity for 1181. The other thing that you've listened to in this call is the word synergistic, actually.

A greater than six more [laughter]. So six months is not usually seen in phase one trials not really does reflect early evidence of clinical activity for for 11 81 Little thing that you listen to this to this call is the word synergistic actually it I'm, usually the opposition to that word, but I could tell you because people will do the math improved but I could.

Dr. Chuck Drake: And I'm usually opposed to that word, but I can tell you, because people don't do the math and prove it, but I can tell you that in kidney cancer, anti-PD-1 and anti-CTLA-4 are indeed synergistic. In terms of complete responses, that is, in the phase three trial of anti-PD-1 in kidney cancer using Navalumab, actually, there were no complete responders. But when that is combined with anti-CTLA-4, the complete response rate ranges between 12 and 15 percent. And Nizer Tanir of MD Anderson has been presenting follow-ups on this data showing that these complete responses, many of them are durable beyond three years. And so in terms of CRs, anti-PD-1 and anti-CTLA-4 in kidney cancer are indeed synergistic. The other thing that Jen pointed out, which is interesting and I totally agree with, is there's a phenomenon that we and others have described called adaptive Treg resistance. That is, when you do something to the tumor, it fights back by increasing Tregs. We've published papers showing this happens with radiation, that this happens with vaccination, and then this also happens in prostate cancer with hormonal therapy.

Tell you that a kidney cancer anti PD, one and it's actually 24 are indeed synergistic in terms of complete responses that is in the phase three trial, if I could you want to kidney cancer using Oh, the volume out actually there were no complete responders, but when that was combined with actually play for the complete response rate.

Ranges between 12, and 15% and nicer to near of MD Anderson has been presenting a follow ups on this data showing that these complete responses. Many of them are durable beyond three years and so in terms of see ours anti PD, one and it's actually 24 kidney cancer or indeed, Oh synergistic.

During the Gen pointed out which is interesting and I totally agree with is theres a phenomena that we and others have described called adoptive T. Reg resistance that is when you do something to the tumor fleets back by increasing to raise we published papers showing the sharpest radiation.

That this happens with vaccination and then this also happens you prostate cancer with hormonal therapy. So if you do self to to the tumor its fights backed by Upregulated T regs and.

Dr. Chuck Drake: So if you do something to the tumor, it fights back by upregulating Tregs, and the idea would be then to deplete those Tregs using a reagent like 1181. 1181 is an interesting molecule, and if you're at all scientifically interested, I really, really urge you to read the cancer cell paper published in 2018 by Waite. Basically, what this molecule is, it's an FC-modified CTLA-4 that has a DLE mutation in the FC portion, which enables us to both bind more strongly to FC gamma R3, and then also it doesn't really care about the different alleles that patients have. So the idea is that this reagent is a much better depleter of Tregs than the other agents on the market. There is competition. I mean, we should be fair.

The idea would be that to deplete those T regs using reagent like a 11 81, eliminating one is an interesting molecule one of your at all so I typically interested I really really urge you to read the cancer cell paper published in 2018 by weight, especially with this molecule is it's an FC modified she actually for the has a deal we mutation.

In the F.C. portion, which enables the book to both by more strongly to FC Gamma our three and then also it doesn't really care about the deferred a wheels that patients have actually so the idea is that this reagent has a much better depleter of T regs and the other agents on them all on the market. There is competition I mean, we should be fair.

Vms has had an anti si play for enough to call slated molecule in the clinic for some time.

Dr. Chuck Drake: BMS has had an anti-CTLA-4 non-fucosylated molecule in the clinic for some time, but activity, clinical activity on that molecule hasn't been presented publicly yet, so we don't really have that data. And there are also other versions of CTLA-4 in development, but this DLE mutation is actually unique, and the data shown in that paper and these early clinical data support it. The one thing I would slightly add to, or perhaps differ from, is that I actually think that the application for a depleting anti-CTLA-4 like this molecule is far beyond IO combinations. I think that combining this agent with chemotherapy, as Brie spoke about, combining it with hormonal therapy and prostate cancer, and combining it with radiation really lends itself to some opportunities. And we're hoping to work with our friends at Agenesis to start some of those trials moving forward. With that, I'll turn it back over to Jen, and thanks for this opportunity.

Activity clinical activity on that molecule has it for presented publicly actually we don't really on how those data. There's also other versions of sequelae for a development, but there's deeley mutation is actually unique and I'm the data showing that paper and these early clinical data or support it it's moving forward or the one thing I would slightly to or perhaps different.

I actually I think that's the application for a depleting anti seasonally for like this molecule is far beyond the Io accommodations I think that combining this agent with chemotherapy as brief spoke about combining with hormonal therapy in prostate cancer and combine it with radiation really.

Lunch, the some opportunities and we're hoping to work with our friends at a genesis to start some of the Genesis starts some of those trials moving toward what that's without I'll turn it back over to Jennifer expose opportunity.

That's a drink. Thank you so much and you can certainly count on that we're looking forward to extending a collaboration without question. Thank you. Thank you again very much we've got exciting plans for each in 11 anyone.

We plan to commercialize this molecule in the U.S. and potentially will consider licensing actually west rights on this in terms of the past the market Rasen development program, we're going to prioritize indication.

Dr. Jennifer Buell: Dr. Drake, thank you so much, and you can certainly count on that, and we're looking forward to expanding our collaboration without question. Thank you. Thank you again very much.

In a relatively large that that are eligible for accelerated approval in the U.S. of aftermarket approach to get the molecule into the market board for patients. This will be through a few different prioritize indications that include but are not limited to PD one refractory.

Dr. Jennifer Buell: We've got exciting plans for Agent 1181. We plan to commercialize this molecule in the U.S., and potentially, we'll consider licensing XUS rights on this. In terms of a path to market and rapid development program, we're going to prioritize indications that are relatively large and that are eligible for accelerated approval in the U.S., a fast market approach to get the molecule into the market for patients. This will be through a few different prioritized indications that include, but are not limited to, PD-1 refractory melanoma This could be the, a single-arm study could form the basis for a first approval with this molecule, and this would, the design of the study could include monotherapy as well as combination therapy, as Chuck mentioned, the criticality of combinations here for durable.

Melanoma.

This could be the a single arm study could form the basis for a first approval with his molecule and this would the design of the study could include a monotherapy as well as a combination as Jeff mentioned that the criticality of combinations here for Steerable curative responses is important and we have the molecules within our own portfolio to do so.

Well also for their pursue combination approvals and I with PD, one and cold tumors. These include microsatellite stable diseases like you've seen responding with endometrial cancer as well as colorectal cancer and of course large prevalent tumors like non small cell lung cancer and prostate cancer, our expectation is the belly company.

And with agent, eliminating one will offer significantly enhanced durability.

Now turning to age and 23 73. This is our novel anti CD 137 molecule. This molecule is designed with important safety and efficacy features as compared to competitor molecules. We presented some of this publicly.

HM 23, 73 is a fully human monoclonal antibody that boost the immune response to cancer cells by enhancing city 137, costimulatory signaling and activated immune cells, both adoptive T cells and an eight NK cells dual targeting of both innate and adaptive immunity.

Dr. Jennifer Buell: We'll also pursue combination approvals with PD-1 in cold tumors. These include microsatellite stable diseases like you've seen responding with endometrial cancer as well as colorectal cancer, and, of course, large prevalence tumors like non-small cell lung cancer and prostate cancer.

Makes us molecule highly attractive target for cancer immunotherapy.

Dr. Jennifer Buell: Our expectation is that belly combination with Agent 1181 will offer significantly enhanced durability. Now turning to Agen 2373, this is our novel anti-CD137 molecule. This molecule is designed with important safety and efficacy features as compared to competitor molecules. We've presented some of this publicly.

Today I am very happy to report that age and 23 73 has dose through the one make for keurig dose cohort with no observed liver toxicity.

And previously liver toxicity was what has hampered our killed one of the competitor molecules.

Furthermore, we've observed durable disease stabilization in patients with ovarian cancer sarcoma, and non small cell lung cancer honest early trial.

We're advancing the combination at we're advancing the molecule into higher dose cohort and in combination with bell filling up while contemplating additional opportunistic combinations with complimentary therapies, such as anti CBLI for combinations.

Dr. Jennifer Buell: HN2373 is a fully human monoclonal antibody that boosts the immune response to cancer cells by enhancing CD137 co-stimulatory signaling in activated immune cells, both adaptive T-cells and innate NK cells. Dual targeting of both innate and adaptive immunity makes this molecule a highly attractive target for cancer immunotherapy. Today, I am very happy to report that HN-2373 dosed through the 1 mg dose cohort with no observed liver toxicity. Previously, liver toxicity was what had hampered or killed one of the competitor molecules.

Now I will turn the call over to Dr., Dan Chan, Dan will summarize import in finding that illustrate the opportunity of novel combination approaches to drive durable and curative responses to cancer, specifically and PD, one or factory cancers. I'll also ask Dan to provide a brief update on our TIGIT molecules and then.

Next steps for allogeneic I am K T cell therapy program.

Then.

Sure John.

Well PD one PD, one antibodies have been a spectacular commercial success.

Only a small portion of patients how sustainable long term license.

Dr. Jennifer Buell: Furthermore, we've observed durable disease stabilization in patients with ovarian cancer, sarcoma, and non-small cell lung cancer in this early trial. We're advancing the molecule into higher-dose cohorts and in combination with balacelamab, while contemplating additional opportunistic combinations with complementary therapies, such as anti-CTLA-4 combinations. Now, I will turn the call over to Dr. Dan Chan. Dan will summarize important findings that illustrate the opportunity of novel combination approaches to drive durable and curative responses to cancer, specifically in PD-1 refractory cancers. I'll also ask Dan to provide a brief update on our TIGIT molecules and the next steps for our allogeneic INKT cell therapy program.

Therefore, there was a substantial need for 13 seizures real rough.

We won't respond to be one more reserves.

We have presented data on patients responding to our Earth on next generation suggested for antibodies.

We're also advancing some important new therapeutics.

Also deliver benefit in selected patient population.

The first decision.

As you all know citrus is shaping up to be a powerful combination partner with PD one antibodies.

Especially in tumors express insurgent.

We have designed to different approaches.

When we targets engine.

Ooh, incorporating our technology vision through I see a generic [noise].

Dr. Dan Chan: Thank you, Jen.

Dr. Dan Chan: Thank you, Jeff. While PD-1 and PD-L1 antibodies have been a spectacular commercial success, only a small proportion of patients have had sustainable long-term care.

[noise] unit was named due to US go from Genentech surgeon.

Reveals that the have no monotherapy.

I would suggest an FC silos is a liability I see competence is important.

So just this over expressed in multiple tumors and there's no ones.

Dr. Dan Chan: Therefore, there is a substantial need for therapies in patients who relapse or do not respond to PD-1 monotherapy. We have presented data on patients responding to our first and next-generation CTLA-4 antigens. We are also advancing some important new therapeutics that may also deliver benefit in selected patient populations. The first is Tidget.

Player in driving resistant to I'm, hoping you want.

And as a result tumors group.

Looking to just with onto bodies like all were more specific TIGIT antibody aegion 13 from southern.

More oriented just by specific Aegion southern seems a southern.

Our mission important immune cells such as she so.

Dr. Dan Chan: And you all know, Tidget is shaping up to be a powerful combination partner with PD-1 Antimicrobial, especially in tumors expressing tigent. We have designed two different approaches to ultimately target TTIP, to incorporate our technology innovation through FCEngineering. You would have seen data at ASCO from Genentech's Tidgets that revealed that they have no monotherapy and suggested that FC silence is a liability, and FC competence is important. Tidget is overexpressed in multiple tumors, and is known to be a key player in driving resistance to anti-PE1. And as a result, tumors grow.

Thank you so the too many types of cancer.

The agenda was the first to discover I'm reports in cancer. So I wonder if you're in 2019, but here's your onto what are you require asked before engagements to promote the ultimate she thought too busy I guess tumors.

Over to Asia 13, 27.

Engineered within a few huntsman and has outperformed all tested competitor onto mornings.

Dr. Dan Chan: Blocking tigets with antibodies like our monospecific tiget antibody, Agent 1327, or our Tidgett bi-specific, Agent 1777, unleashes important immune cells such as T-cells and NK-cells that kill many types of cancer. Agenus was the first to discover and report in cancer cells and the AACR in 2019 that tiget antibodies require F-seq co-engagement to promote optimal T-cell Our Tidget, Agent 1327, is engineered with this FC enhancement and has outperformed all tested competitor antigens and showed superior T-cell activation when combined with PD-1 or LAG-3 antagonists for AUX40 or CD137, Agenus. PIDGET is an ideal combination partner for addressing known resistance mechanisms in current checkpoint therapy and with the potential to provide a superior response. In addition to the superior functions demonstrated against tested competitors, our molecule was designed to 1. improve anti-tumor activity similar to the robust activity with our FC engineered agent 1181 that has shown remarkable activity in early clinical trials. Our preclinical data with our digits also show superior tumor killing compared to competitor molecules, and be an optimal combination partner for anti-PD-1 antibodies for more potent tumor killing, particularly for tigit-expressing tumors, including non And three, expand the population of patients who will benefit from TIGIS by targeting all genetic polymorphic variants of a particular Fc receptor.

I'm showing superior she's a lucky vision when combined with PD, one for luxury of others.

For ox, 41st do you want from southern others.

Older says it is an ideal combination partner for addressing no one would resistance mechanisms current checkpoint therapy.

The potential to provide for responses.

In addition to the superior functions demonstrated a gets tested competitors or molecule with design to ones.

Improve antitumor activity similar to the robust activity with or FC engineered agency love any one.

A short remarkable oxygen early clinical trials.

Over preclinical data with older tonnage is also show superior tumor, killing compared to components are more tools.

Two.

Be an optimal combination partner for anti PD, one antibodies were more potent tumor killing.

Particularly for digits expressing tumors, including non small cell lung cancer.

I'm three expanded the population of patients who benefit from TIGIT by targeting all genetic polymorphic variance of that particular FC receptor.

So just has also been executed as important target.

We're coming resistance to anti PD one therapy.

For by specific to just Aegion 17 77.

It was designed to be use of monotherapy for tumors, which are all the responsive to PD one antibodies.

Hey, Jim 17, 77 is a first in class. So just by specific that's coal as hard as a mother inhibitors sector not just the schools, but also expressed on T cells NK cells.

We discovered that post harvest incision using or by specific.

Dr. Dan Chan: Tidget has also been implicated as an important target for overcoming resistance to anti-PD-1 therapy. Our bispecific tiget, agent 1777, is designed to be used as monotherapy for tumors which are unresponsive to PD-1 antibodies. Agent 1777 is a first-in-class tiget bispecific that co-targets another inhibitor receptor, not yet disclosed, but also expressed on T-cells and NK-cells. We discovered that co-targeting TIGIT using over-body specifics provides superior immune activation.

Right.

Your your immune activation.

Our preclinical data demonstrate aegis 17, 77 can get important therapy in TV, one relapse restructuring tumors.

[noise] or pipeline is uniquely designed the broadens the therapeutic reach of new therapy.

Enable curative combinations.

Her most recent visa presents an easy are this year.

I'll leave it to a rational for a complimentary pipeline of therapies.

Utilizing clinically relevant tumor models that every fracturing curved TV, one and security for engines.

Dr. Dan Chan: Our preclinical data demonstrate Agent 1777 can be an important therapy in PD-1 relapsed and refractory. Our pipeline is uniquely designed to broaden the therapeutic reach of immunotherapy and enable curative combination. Our most recent data presented at AACR this year validated our rationale for a complementary pipeline of therapies, utilizing clinically relevant tumor models that are refractory to current PD-1 and CTLA-4 agents. We demonstrated that next-generation CTLA-4, like Agent 1181, promotes superior single-agent efficacy and more effective combination activity than the current approach. Notably, we reported curative responses in difficult-to-treat tumors with next-generation CTLA-4 in combination with PD-1 and or adopted T-cell therapy or QS21-containing neoantigen vaccine. These data highlight the attributes of Agent 1181, specifically enhanced T-cell priming, intratumoral Treg depletion, and Superior T-cell memory response.

We've demonstrated that much generations. Each other for like you did you ever maybe one for most superior single agent up at the C.

I am more defensive combination onto the team the current approaches.

Notably we reported curative responses.

Difficult to treat tumors with next generation security for in combination with PD one.

I'm sort of off the T cell therapy.

Qs 21, continuing your antigen vaccine.

These days a highlight the attributes of age at 11 anymore.

Specifically and how does she so private.

Intra tumoral she's rugs accretion.

I'm superior she still remember responses [noise].

We further demonstrates is assistance with her clinicals isn't visited our school.

Pure your responses and populations that respond poorly.

First generation circular for because of a genetic predisposition invested Guo our receptor three or see 16 illegal stuff.

We review for the first time.

Powerful combination potential of next generation city other for on PD, one with Ironkey oxygen therapy.

Hair in a highly checkpoint refractory long metastasis models.

We show the combinations with I M Cubed GTAT Bijan therapy resulted in a robust on sexist quitters tourism Hello.

Dr. Dan Chan: We further demonstrated, consistent with our clinical data presented at that school, superior responses in populations that respond poorly to first-generation CTLA-4 because of a genetic predisposition to FC-gamma-R receptor 3A or CB16 allele status. We revealed, for the first time, the powerful combination potential of next-generation CTLA-4 and PD-1 with INKT activating therapy, here in a highly checkpoint refractory low metasta We show that combinations with INKT activating therapy result in a robust and effective clearance of tumors in the lung. As you are aware, the efficacy of cell therapy has been primarily active only in liquid cancers, We show that INKT therapy, in combination with our checkpoint portfolio, can significantly broaden the therapeutic benefits and capabilities beyond those of our competitors.

As you're aware.

We could see of cell therapy has been primarily up to only liquid cancers.

Sure.

We show the I M T therapy in combination with our checkpoint portfolio can significantly broadened the therapeutic benefits on capability beyond got over competitors.

Do you use exciting findings demonstrating the power of our portfolio.

Further volumes are unique position in the field, where it comes to pursuing preservative combination therapy.

As Jennifer highlighted we are already commenced combination trials with aegis 11 anymore.

Under already seeing early signs of clinical basis [noise].

I'll now turn the call over to Jennifer an update on the progress around him he for rooms.

Thank you very much Stan.

Very soon we hope to we expect to announce the initiation of a clinical trial using our allogeneic I am K T cells to treat patients with moderate to severe coven 19. This trial will be conducted.

Dr. Dan Chan: These exciting findings demonstrate the power of our portfolio and further validate our unique position in the field when it comes to pursuing co-occurring combination therapies. As Jennifer highlighted, we have already commenced combination trials with Agent 1181 and are already seeing early signs of clinical benefits. I will now turn the call over to Jennifer to provide an update on the progress of our IMKT programs.

To start at New York Presbyterian Hospital, how we've already cleared the I.N. Dean and are working with the institution now to launch the trial within the next very near term.

I am K T cells or invariant natural killer T cells are unique cell type.

Combined to features a both times of the immune system the T cells and NK cells, both the adaptive and innate immunity.

Dr. Jennifer Buell: Thank you very much, Dan. Very soon, we expect to announce the initiation of a clinical trial using our allogeneic INKT cells to treat patients with moderate to severe COVID-19. This trial will be conducted to start at New York Presbyterian Hospital. We've already cleared the IND and are working with the institution now to launch the trial within the next very near term. INKT cells, or invariant natural killer T-cells, are a unique cell type that combines the features of both arms of the immune system, the T-cells and NK-cells, both adaptive and innate immunity.

Data in animal models similar to Sars kill two infection show the increasing the frequency of I am K T cell reduce viral shedding.

Prevented inflammation, driven lung injury and demonstrated viral clearance.

These are all particularly important attribute any attempt to overcome cobot 19.

Beyond Kelvin 19, these cells have great potential in mitigating cancer and Agenuss is advancing clinical trial for patients with cancer planned for later this year.

Again those trials are also a sta cleared to launch the I am I to launch that clinical trial and now we're just working with the hospital on readiness and resource availability during the pandemic. So we expect that that trial will start up very quickly certainly in the second half of this year.

Dr. Jennifer Buell: Data and animal models similar to SARS-CoV-2 infection show that increasing the frequency of INKT cells reduces viral shedding, prevents inflammation-driven lung injury, and demonstrated viral clearance. These are all particularly important attributes in the attempt to overcome COVID-19.

<unk>.

[noise] importantly scientist from Agenuss presented data most recently, Dan highlighted some of that.

Dr. Jennifer Buell: Beyond COVID-19, these cells have great potential for mitigating cancer, and Agenus is advancing clinical trials for patients with cancer, planned for later this year. Again, those trials are also FDA cleared to launch the clinical trials, and now we're just working with the hospital on readiness and resource availability during the pandemic. So we expect that that trial will start very quickly, certainly in the second half of this year. Importantly, scientists from Agenus presented data.

But a gentle I NK teas can penetrate tissues the home to the important tissues, where the action is necessary, giving them a critical advantage to target solid tumor not served by available cell therapies.

I am K piece can kill cancer without requiring genetic mean manipulation. This is really important we can eliminate significant cost and capacity constraint.

Dr. Jennifer Buell: Most recently, Dan highlighted some of this, that Agentis INKPs can penetrate tissues; they hone in on the important tissues where the action is necessary, giving them a critical advantage to target solid tumors not served by available cell therapies. INKPs can kill cancer without requiring genetic manipulation. This is really important. We can eliminate significant costs and capacity constraints that are required to modify typical cell therapies through genetic modification. We don't have that.

That are required to modify typical south therapies to genetic modification, we don't have that a lot of fight I M. T. T cells target a specific lippitt antigen CD, Wendy on tumors and tumor supporting cells.

And I am K T cell activity can be augmented by a lit bit like in also known as a whole glaxo bear in mind.

The combination of checkpoint antibodies and activated I'm K T cell triggering therapy shows curative potential and PD one refractory models as Dan just reported to you now that support our clinical plans going forward to go beyond take cell therapies beyond hematologic tumors and.

Dr. Jennifer Buell: Unmodified INTP cells target a specific lipid antigen, CD1D, on tumors and tumor-supporting cells, and INKT cell activity can be augmented by a lipid ligand, also known as alpha-galactosaromide. The combination of checkpoint antibodies and activated INKT cell triggering therapy showed curative potential in PD-1 refractory models, as Dan just reported to you now. That supports our clinical plans going forward to go beyond, take cell therapies beyond hematologic tumors and move into solid tumors, specifically in combination with active checkpoint modulating antibodies. Agenus has the benefit of a very well-designed portfolio of checkpoint antibodies, cell therapy, and vaccines, which gives us enormous flexibility to develop these novel combinations, with curative potential for patients with cancer and infectious disease at a significant cost advantage. I'm really excited to share with you as these trials continue to mature in the clinic. I'll now turn the call back over to Garo to summarize our near-term catalyst.

Moving on to solid tumors, specifically in combination with active checkpoint modulating antibodies.

Agenuss has the benefit of a very well design portfolio of checkpoint antibodies cell therapy, and vaccines, which gives us enormous flexibility to develop these novel combination.

With curative potential for patients with cancer and infectious disease at a significant cost advantage I'm really excited to share with you as these trials continue to mature in the clinic.

I'll now turn the call back over to grow to summarize our near term catalyst.

Thank you for every one oldest speakers I think the this phenomenal job both outlining.

Well, we have ongoing.

And I know that at times.

The enormity on what we have.

Garo H. Armen: Thank you, everyone. All the speakers, I think, did a phenomenal job of outlining what we have ongoing. And I know that at times the enormity of what we have can be a little confusing. It's a lot.

Gets a little confusing it's a lot.

And then but don't intimidated by.

The enormity of the immune system.

And the complexity of cancer.

Garo H. Armen: But don't be intimidated by the enormity of the immune system. And the complexity of cancer is such that it requires, if we want to battle this disease properly, it requires an enormous army of capabilities, enormous military capabilities, if you will, immune military capabilities to be able to battle this problem. For those of you who are interested in digging into it a little bit more, we have an excellent, very well-written book by Laurence Samporyak that we have in stock here. If you contact Amber Henson, you will get a copy of it.

He is such.

Yeah. It requires we're gonna come from this disease properly.

She requires an enormous army or capabilities enormous military capabilities. If you will immune military capabilities to be able to fat holdings from for those of you who are interested in digging into it a little bit more we have.

And excellent very well written book.

Bye.

Lawrence from Korea that we inventory here.

If you contact Amber Hanson, our you'll get a copy of it or it will be a gift from us to you.

Garo H. Armen: It will be a gift from us to you. Particularly, the first lecture of that book outlines the way the immune system works beautifully. I'm getting back now.

Particularly the first lecture on Red Oak outlines the waiting years system works beautifully.

Getting back now.

Garo H. Armen: All of what you've heard so far today and what you haven't yet heard sets us up for an exciting second half of this year and beyond. Among critical path items for us is to initiate our BLA filing for Bustillamab and conclude our discussions with the FDA on the confirmatory trial design, which will be our obligation to get full approval down the road for cervical cancer in an earlier disease setting, for Bostelumab alone and for Bostelumab plus Xerflimzumab. It's a mouthful, I know that.

All of what you heard so far today.

And what you haven't get hurt.

Sets us up for an exciting second half of this year and beyond.

Among critical path items for us is to initiate our be late filing for most of them up.

And conclude our discussions with the FDA on the confirmatory trial design, which will be our obligation to get full approval down the road for cervical cancer in an earlier disease setting.

For a while still in my alone and for Boston them up plus there's little room.

Hi, Jim Awesome, I know that based on the outcome, albeit a few discussion.

Garo H. Armen: Based on the outcome of the FDA discussion, we will be prepared for filing, not just one, but the combination of Bacillimab and Zoliferolimab in patients with refractory cervical cancer, in addition to these exciting plans. We will also present data, as Jen spoke about and I mentioned earlier, at upcoming medical conferences and scientific conferences this year on Balfour-Limaux alone, both filaments alone or in combination with the filament.

We will be prepared for filing mattress, one by the combination or by some of them out as all the for women are being patients with refractories cervical cancer.

In addition to these exciting plans. We will also presented data as John spoke about I mentioned earlier and upcoming medical conferences in scientific conferences this year on but still a milestone.

Boston them in combination with so it was really map.

We will present further updated data on agent 11, maybe one or multipurpose next generation steward for molecule.

Garo H. Armen: We will present further updated data on Agent 1181, our multi-purpose next generation CTLA-4 molecule. We also plan to advance trials for extended development with Valley's Alley in indications beyond service, and that's geographically, not just in the U.S. but beyond.

We also plan to advance trials for expand this development with valleys Sally in indications beyond service.

And that geographically not just in the U.S., but yeah.

Garo H. Armen: We will also initiate combination trials of Agen 2373, R41VB, anybody, and Agen 1223, our bispecific Treg intratumoral Treg depletor. Dr. Drake talked about the importance of Tregs, and this particular molecule is an intratumoral acute Treg depletor, which is where you want the Treg depletion to be. Because if it's systemically depleted, you may have a counter-autoimmune issue associated, and with both Philip Mapp and others in our portfolio. We will advance our proprietary process development, as Jen mentioned, for a sustainable supply of QS21. Finally, we will launch clinical trials of allogeneic INKT cells in patients with COVID-19 and separately for cancer.

We will also initiate combination trials old age and 23 73 or four one we be anybody.

And age and OLED 12, 23, Oh by specific to Reg intra Tumoral Kubrick depleter that the drinks talked about the importance of T. Regs and this particular molecule is an intra tumoral Q2 rate deplete.

Which is where do you want the T Reg depletion to be because if it's systemically depleted you may have a counter autoimmune issue associated.

[noise] and with both some of them up and others in our portfolio.

We will advance our proprietary process development as Jim mentioned, four as sustainable supply of Qs 21.

Finally, we will launch clinical trials or allergenic Ironkey T cells in patients with core with 19.

And separately for cancer.

Garo H. Armen: Taken together, we're excited for the trajectory of our company, your company, in the second half of this year and beyond. Our hard work and your patience should position Agenus as one of the most innovative progressive growth companies in our industry. That concludes our formal remarks, and I'll turn it over to Jason now. I think we have a process for incoming questions.

Taken together, we're excited for the trajectory of our company your company in the second half of this year and beyond.

Although our hard work and your patience.

Position Agenuss as one of the most innovative.

Progressive growth companies in our industry that concludes our formal remarks, and I'll turn it over to Jason now I think we every process for incoming questions.

Thank you, we'll now begin the question answer session.

Operator: Thank you. We will now begin the question and answer session. Saskia, question. You may press star then 1 on your touch-tone phone. If you are using a speakerphone, please pick up your handset before pressing the button.

The question you May Press Star then one on your Touchtone phone.

If you're using they speakerphone, please pick up your handset before pressing the keys to withdraw your question. Please press Star then too.

Mayank Mamtani: To withdraw your question, please press star, then 2. The first question comes from... Mayock, Mamtani from B Reilly FBR. Good morning. Thanks, team, for taking my question. Congrats on the progress across, seems like several modalities you have in your portfolio. Just quickly on the 1181; great to see the partial response converting to PR. Jen, could you maybe talk about these nine pending scans you have? You know, what qualitative color on what tumor types and is this going to be some data presented at ESMO in October?

The first question comes from.

May or may appear any from B. Riley FBR.

Good morning, Thanks, Dean religion that question congrats on the progress across seems like seven modalities you have in your portfolio just quickly on the one when you do on the need to see the boxes funds converting to be Oh, Dan could you maybe talk about these nine bending Scott do you have.

You know what just qualitative color on what do you might dives and is it's going to be some data presented at ESMO in October.

Dr. Jennifer Buell: Hi Mayank, thanks very much for the question. So regarding the PendiScan, these are patients who are now, we look, patients are scanned every six weeks. And so, therefore, we get a sense of what's happening with their tumor dynamics over that period of time. And what our clinical team, and Dr. Ana Viatek is here with us as well, what they will present effectively is a series of these waterfall plots that allow us to watch the tumors. Now what we have seen over time, such as for this patient with durable ovarian, a durable response, for over 18 months with ovarian cancer, when you're actually looking at the dynamics of that patient's scan, you're actually seeing that the tumor, it's, you know, tumors, they're never not moving in one direction or another. They're either growing or shrinking, and what we're seeing is this continuous shrinking or a negative radiologic finding, and as we watch that, we see that there may be a point at which that could trigger requirements to meet the RECIS 1.1 requirements for consideration as a partial response or a complete response.

Hi, Mike Thanks, very much for the question. So regarding dependencies and these are patients now we luck patients are scanned every six weeks and and so therefore, we get a sense of what's happening with their tumor dynamics over that period of time and what our clinical team and that's kind of the attack is here with us as well.

Well, what they will present effectively is a series of these water pots that allow us to watch the tumors now what we have seen over time, that's just for this patient with a durable ovarian a durable response.

For over 18 months with ovarian cancer, when you're actually looking at the dynamics of that patient scan. Your act you're seeing that the tumor. It's you know tumors, they're never I'm not moving in one direction or another there either growing or shrinking and what we're seeing is this continuous shrinking or a negative.

Our radiologic, finding and as we watch that we see that there maybe a point at which that can shrink or requirements to meet the recessed 1.1 requirements for a consideration is a partial response or a complete response.

So we are watching these scans of these patients tend to see where they are with respect to their tumor dynamics and conversion to responses. So there are a couple of upcoming medical conferences. ESMO is certainly one is you'd mentioned, there's also sissy and there are a few other conferences and we do plan to present data.

Garo H. Armen: So we are watching these scans of these patients to see where they are with respect to their tumor dynamics and conversion to responses. So there are a couple of upcoming medical conferences. ESMO is certainly one, as you've mentioned.

Mayank Mamtani: There's also CITSE, and there are a few other conferences. And we do plan to present data on our cervical cancer program, as well as on 1181, at upcoming medical conferences. Now, of course, we can't disclose that conference as of yet. Abstracts are in review, as you know, the process here. So we will inform you as soon as we can where that data will be presented. But yes, you can expect clinical updates on our LEAD programs, including 1181.

On our cervical cancer program.

As well as on 11 81.

At at some of it it Oh and upcoming medical conferences now of course, we can't disclose that conference as of yet abstracts are in review as you noted that the process here. So we will inform you as soon as as we can where that data will be presented but yes. We you can expect clinical updates.

On our lead programs and including 11 anyone.

Great. Thank things would add litigation and then you don't do got his comment about a lot going on it and especially with.

Early in one when they do one how do you strategically think about it. So it is taking a step back is it.

Dr. Jennifer Buell: And then on, you know, to Garo's comment about a lot going on, and especially with ZALI and 1181, how do you strategically think about it? So, just taking a step back, is it stratification by allele? Is it, you know, narrow versus broader tumor types? Like, how are you thinking about the two, given both are now demonstrating very good clinical activity?

Startup occasioned by L., you is that no matter, which is why don't you guys. Like how are you thinking about the do you have been a board are now demonstrating.

Very good clinical activity.

Thanks, very much ran very important question here, we are seeing out in the responses and just to reiterate for age and 11 81, we have a complete response that we've reported on and now a pet complete response. So two of those patients have responses here as well as the long term durables stable disease stabilization.

And that we've observed now in those responses. What we are seeing is that those patients have the mutation and they CD sixteena Leon data presented from us as well as others have demonstrated that those patients aren't are unable are unlikely to respond to a first generation therapy. This does allow us to leverage this particular genetics.

Dr. Jennifer Buell: Thanks very much, Ryan. A very important question here. We are seeing now in the responses, and just to reiterate, for HN1181, we have a complete response that we've reported on and now a partial complete response. So two of those patients have responses here, as well as the long-term durable disease stabilization that we've observed. Now in those responses, what we are seeing is that those patients have the mutation in their CD16 allele, and data presented from us as well as others have demonstrated that those patients are unable or unlikely to respond to a first-generation therapy. This does allow us to leverage this particular genetic biomarker as a consideration for stratification.

Biomarker as a consideration for strategy stratification.

Now there are tumors and of course valleys alley, our mature assets there a in preparation for BLE filing.

And and we have generated hundreds of patients worth of data with these molecules, we have a significant opportunity to continue to expand the development of these molecules already these validated io agents and tumors, where we know that there is a activity with the citilane floor and or.

PD one [noise].

Hi, and these approaches these tumor indications expanding in these with valleys Sally allows us a few things generate data and larger market opportunities that that will support inclusion into NCCN guidelines that will allow physicians access to our agency prescribed for their patients.

Dr. Jennifer Buell: Now, there are tumors, and of course, bali-zali are mature assets. They're in preparation for BLA filing, and we have generated hundreds of patients' worth of data with these molecules. We have a significant opportunity to continue to expand the development of these molecules already, these validated I.O. agents in tumors where we know that there is activity with CTLA-4 and or PD-1. And these approaches, these tumor indications, expanding these with bali-zali allows us a few things. Generate data and larger market opportunities that will support inclusion into NCCN guidelines that will allow physicians access to our agents to prescribe for their patients, as well as, and of course, further expanded data for approval. Now, these are very quick indications because we already have a path laid out for us.

As well as then of course further expanded data for approval. Now. These are very quick indications because we already have has laid out for us. So we don't want to lose the opportunity to take advantage of valleys alley, and indications where they know that will work now with respect to age and 11 81, we.

Have PD, one refractory cases in which we believe this molecule could have pronounced activity, particularly in patients with the polymorphism that allows for some enhancement for identification of response our teams overall.

Critically looking at every patient in our child and of course, that's the big goal is to identify patients most likely to respond and include them on the therapy that they are most likely to have a response do.

And a low hanging fruit for us of course is a city 16, LDL patients, it's opportunistic and it allows us to differentiate and have lifecycle management of our first generation as follows our next generation therapies.

Dr. Jennifer Buell: So we don't want to lose the opportunity to take advantage of bali-zali in indications where we know that it will work. Now, with respect to HN1181, we have PD-1 refractory cases in which we believe this molecule could have pronounced activity, particularly in patients with the polymorphism that allows for some enhancement in the identification of response. Our teams overall are critically looking at every patient in our trials, and, of course, the goal is to identify patients most likely to respond and include them in the therapy that they are most likely to have a response to. And a low-hanging fruit for us, of course, is a CD16 allele patient. It's opportunistic, and it allows us to differentiate and have life-cycle management of our first-generation as well as our next-generation therapies.

They have them and if I can just squeeze in the final question around your bought Midroll gods and its beside question that I'm, a united be Threeseventy that had the collaboration with Goliat and then also if you could comment on U.S. to anyone including I think some comments around.

But yeah deal was that he is good I've.

Been talking about the I do end, which I think you ask anyone has bought a company in it.

Dispute just remind us the the.

Specific to be the guy in the world that is going on and what the.

Your partners. It you know as you go gases and dozens of that putting out more data.

Sure.

As far as our partnerships are concerned and as you said a lounge.

We have deal yet and others you'll be hearing.

Some near term development I think on milestones that we may reach with our existing partners. That's an ongoing thing.

Mayank Mamtani: Very helpful. And if I can just squeeze in the final question about your partner programs, And it's a two-part question around, you know, 2373, which has the collaboration with Gilead. And then also, if you could comment on QS21, including, I think, some comments around, you know, the AS01 that GSK has been talking about the adjuvant, which I think QS21 has a component in it. Can you just remind us, with some specificity, the kind of work that is going on and what terms you have with your partners, you know, as you progress this in terms of putting out more data?

And going forward as our portfolio personal license in terms of generating data.

For example data that we're seeing on 11 81.

Our next Gen multipurpose utility for.

That makes the data we're seeing makes it molecules very valuable.

In fact, you know if you look at all funds, who last five years, a we believe.

Garo H. Armen: Sure. I mean, as far as our partnerships are concerned, as you said, Mayank, we have Gilead and others. You will be hearing some near-term developments, I think, on milestones that we may reach with our existing partners. That's an ongoing thing.

Our MCN and eliminating one is one of the most important breakthroughs in Ohio.

I also believe of course, there, that's where we followed with our attention.

23, 73, and so what I mean, all these molecules that share a very important engineering design component based on our knowledge of the field knowledge will buy allergy knowledge of cancer to use them.

Garo H. Armen: And going forward, as our portfolio crystallizes in terms of generating data, For example, data that we're seeing on 1181, our next-gen multipurpose CTLA-4, makes that molecule very valuable. In fact, you know, if you look at developments in the last five years, we believe our FC Enhanced 1181 is one of the most important breakthroughs in I.O. And we also believe, of course, that that's going to be followed by our tingent and 2373 and so on. I mean, all of these molecules that share a very important engineering design component based on our knowledge of the field, our knowledge of biology, and our knowledge of cancerous diseases. All of these things make our molecule, ones that have not come about by chance but have been specifically designed to do certain things.

All these things make.

Our molecules why does that have not come abide by chance.

And specifically designed to the short answer.

So that's very exciting for us now because we do not have a global reach as a company.

Well, we won't concentrate our commercialization efforts in the U.S. So going forward you can expect us to increasingly have a higher proportion of all our portfolio.

And for your West rights.

And licensed for X yours.

Sure that's going to read the path forward for us and in our discussions with companies generally everybody wants square the U.S. component, but it's also clear Brown as you know that'd be ex us cancer market is growing.

Garo H. Armen: And so that's very exciting for us. Now, because we do not have a global reach as a company, we will concentrate our commercialization efforts in the US. So going forward, you can expect us to increasingly have a higher proportion of our portfolio retained for US rights and licensed for ex-U.S. purposes. So that's going to be the path forward for us. And in our discussions with companies, generally, everybody wants to have the U.S. component, but it's also clear, Mayank, as you know, that the ex-U.S. cancer market is growing, led by China, but also other geographies. Hence, the ex-US market, in terms of the value that it will generate for our collaborator partners of the future, will become much more significant. In terms of QS21, As I have said, this is, again, another complex subject. People have asked me the question, for example, whether GSK made one of their adjuvant systems available upwards of about a billion doses for COVID vaccines. And the question that was asked was, does it contain QS21? And if not, why not?

And my China, but also other geographies, so hence X you watch market interim Joel the value day will generate four oh.

Operator partners over the future will become much more significant.

In terms of Qs 21.

So as I've said I mean this is again then other complex subject.

People are asking me to question for example, a GSK made a one of their adjuvants systems available upwards over bought it billion doses for over the vaccine.

And the question that wasn't pass was does it contains Qs 21.

And if not why not.

So the answer that question is it does not contain Qs 21.

And the reason is very simple you cannot make enough Qs 21 today to supply billion doses or anywhere near it gives you a make 100 million those excuse me.

So what does that do that means that we're obligated.

Garo H. Armen: So the answer to that question is, it does not contain QA. And the reason is very simple; you cannot make enough QS21 today to supply a billion doses or anywhere near it. You can't even make a hundred million doses. So what does that do?

With a high Sentinel responsibility to make sure that we explore.

Renewable sources raw material for making Qs 21 cell phone.

Very important you realize Qs 21 supporting has been in well over one I'm, sorry 10 million people.

Garo H. Armen: That means that we're obligated... with a high sense of responsibility to make sure that we explore renewable sources of raw materials for making QS21's opponent, and it's very important that you realize QS21's opponent has been used by well over one, I'm sorry, 10 million people. There is no... QS21 from any other source that I know that has that many people treated or vaccinated. Now, that's why, for example, our QS21 subcomponent has proprietary components in terms of manufacturing, which are known to us and known to GSK. No one else is.

There is no Qs 21 from any other source that I know that has that many.

People treated or vaccinated.

Now that's why for example, how Qs 21, so has proprietary components in terms of manufacturing, which are known to us.

And known to GSK.

No one else no one else has rights to the proprietary manufacturing.

Garo H. Armen: No one else has rights to that proprietary manufacturing process. Now, along with that proprietary manufacturing process... We are active, working on Upscaling, from an engineering perspective, a renewable raw material that Jen talked about. It's a, that will be the feedstock for making QHP. That's what we're working on. Now, we've gone through the scientific validation of that process. So we know that, for example, QS21's opponent that we make from that process is exactly the same profile as the traditional QS21 supponent that we make from natural tree bark.

How long winded proprietary manufacturing process.

We are actively working on.

[noise] up scaling.

From an engineering perspective.

A renewable raw material that Jim talked about.

Its a.

I am so line.

That will be the feedstock for making Qs 21.

That's what we're working on now we've gone through the scientific validation all that process. So we know that for example, Qs 21. This opponents that we make from that process is exactly the same profile as the traditional Qs 21 supported that we've made.

On the natural treat Bart.

Garo H. Armen: So that's been done. The next step is simply engineering. Scaling up. And of course, science is behind us. Engineering is ahead of us. And people say, well, so why can't you scale up tomorrow? It's not that simple. Because plant cells take time to grow.

So that's been done.

The next that.

It's simply engineering.

Scaling up.

Of course size is behind US engineering is headless.

And people have also why can't you scale up tomorrow.

The fact that simple because.

Trends sales pace.

To go and so scale up takes a little bit of effort as well, but bear with us from our essential responsibility. We won't do there's a we will upscale and we will scale up.

Garo H. Armen: And so scale up takes a little bit of effort as well. But bear with us. From our sense of responsibility, we will do this. We will upscale, and we will scale up. Now, importantly... I should...

Now importantly.

[laughter].

Garo H. Armen: Some of the vaccines out there, there are something like five lead COVID-19 vaccines that have been advertised, and of those five, for that we know, don't have an adjuvant in their formulation. So if those four, or even the fifth one, don't perform exactly as we all hope they will perform, and one needs to boost its activity, For example, in Shingrix, you have 90% plus efficacy; in a similar vaccine for shingles, you have 50% efficacy. One of the key differences between the two is that Shingrix contains 2S-21's component.

Some older vaccines out there or something like five lead coal is 19 vaccines that are being advertised.

And all of those five.

For that we know.

I don't have an excellent and their formulation.

So if.

Doors for or even dependable.

Don't perform.

Exactly as we all hope they will go for it.

If that happens.

And one needs to boost it activity for example in Shingrix, you have 90% plus efficacy.

And it's similar vaccine.

For shingles, that's 50% of.

One of the key differences between the two is a 90% plus aftertreatment enforcement once upon the other one doesn't show.

Garo H. Armen: The other one doesn't. So should those COVID vaccines need help in the future because they don't perform as we all hope they will, then we would like to make sure that for this pandemic or for future pandemics, we will be ready. That's the purpose of wealth. Does that answer your question, ma'am?

Sure.

Dawn.

Corporate vaccines need help in the future because they don't perform as we all hope. They will then we would like to make sure that for this endemic or for future Pandemics, we will be ready.

That's the purpose or what.

And then after your where anywhere.

Mayank Mamtani: Yes, and what we learned earlier this week, the adjuvanted vaccines are definitely, you know, performing relatively better. So I am absolutely looking forward to, you know, more updates from you on that, and I appreciate the broader context. Thank you so much.

Yes, and what we learned earlier this week a you know the I do ended vaccines.

Definitely no bombing relatively better so absolutely looking forward do you know more updates from you on that and appreciate the Garda color. Thank you so much in and I can actually be taking my good.

Operator: I appreciate you taking my question.

Operator: Thank you. Again, if you have a question, please press star, then 1. Next question is from Matt Phipps from William Blair. Please go ahead. Hi, this is Hunter on format. Thanks for taking my questions. Um, just first, I wondered about 2373. You mentioned that there was no liver toxicity observed. Um, I was wondering if you could provide some color on sort of any other adverse events and the tolerability there.

Thank you.

Again, if you ever question. Please press Star then one.

Next question just from that fits from William Blair. Please go ahead.

Right that's in the corner on for Matt and Thanks for taking my question just for a wandered off on a 23 73.

You mentioned that there is no liver toxicity observed.

I was wondering if you could provide some color on a sort of any other adverse event.

The tolerability there.

Hunter: Thanks very much for your question. The molecule is really quite tolerable, so we have not had any other deleterious adverse events. In fact, no adverse events have really emerged beyond.

Thanks very much for your question at the molecule is really quite tolerable.

So we have not no other ideally serious adverse events no adverse events have really emerge beyond I have Anna via tickets here as well she can speak to to this and I guess from your feedback and maybe just a little color on the the safety of them only go so far the safety profile, that's been a pretty predictable.

Dr. Jennifer Buell: I have Anna Viotek here as well. She could speak to this. Anna, from your feedback, maybe just a little color on that.

Anna Viotek: So far, the safety profile has been pretty predictable and pretty mild, with no unexpected events consistent with the mild conditions.

And Ah pretty mild no unexpected events, so consistent with the with the and mild and moderate or how does the event so immune mediated stuff nothing comfortable ordinary thank you very much.

Anna Viotek: Thank you very much.

Hunter: Thank you. And then I was also wondering, um, about the Dr. Reubenson-Balasalli study. I was wondering what the tolerability was looking like there.

<unk>.

Thank you and winter was also wondering I'm on the Ducks and rubicam about selling study I was wondering what the tolerability with looking like there I know, there's always part patients book.

Operator: I know there's a lot of questions. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah.

Gary.

So I want to see if dr. pretty well he is still on the line I know that she had a clinic requirements starting seemed pretty are you still on the line.

Operator: but I'll leave that to Siri.

Dr. Jennifer Buell: So I'm going to see if Dr. Brie Wilkie is still on the line. I know that she had a clinic requirement starting. Brie, are you still on the line?

Yeah, I'm still here could you repeat the question though.

No two are asking on or what the Tolerability tolerability of the Doxorubicin BOLI Valley.

So he was looking like.

Dr. Brie Wilkie: Yeah, I'm still here. Could you repeat the question, though?

So again, it's a little early we're actually this is our our safety lead in Korea with the six patients, but I will say that at least today, we haven't seen any prohibitive deal teams that are limiting the combination.

Hunter: Yeah, I was just asking what the tolerability of the Doxorubicin Molly's Alley study was looking like.

Dr. Brie Wilkie: So, again, it's a little early. We're actually in our safety lead-in period with the six patients, but I will say that, at least to date, we haven't seen any prohibitive DLTs that are limiting the combination.

Okay. Thank you very much.

Sure.

There are no more questions in the Q.

This concludes our question and answer session.

I'd like to turn the conference back over to Dr. Garo Armen.

Dr. Brie Wilkie: Okay, thank you very much. There are no more questions in the queue. This concludes our question and answer session. I'd like to turn the conference back over to Dr. Garo Armen for any closing remarks. Thank you very much, Jason.

For any closing remarks.

Thank you very much Jason and thank you very much for everybody for joining us on this occasion, we look forward to shore up further our age and.

We'll keep you.

In form so everyone could be at least as excited as we are thank you.

Thank you.

Garo H. Armen: Thank you very much, Jason, and thank you very much to everybody for joining us on this occasion. We look forward to further updates, and we'll keep you informed so everyone can be at least as excited as we are. Thank you. Thank you.

[noise] [noise] conference has now concluded. Thank you for attending today's presentation you may now disconnect.

[noise].

Operator: The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.